Inhibitors of histone deacetylase

ABSTRACT

This invention relates to compounds and methods for the inhibition of HDAC enzymatic activity. More particularly, the invention provides for compounds of formula (I), (I) and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein L, M, n, R, W, X and Y are as defined in the specification.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. provisional application No.60/985,060, filed Nov. 2, 2007.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to compounds for the inhibition of histonedeacetylase (HDAC). More particularly, the invention relates tocompounds and methods for inhibiting HDAC enzymatic activity.

2. Description of Related Art

Histone deacetylases are involved in the epigenetic regulation of geneexpression through chromatin remodeling. In eukaryotic cells, nuclearDNA associates with histones to form a compact complex called chromatin.The histones constitute a family of basic proteins which are generallyhighly conserved across eukaryotic species. The core histones, termedH2A, H2B, H3, and H4, associate to form a protein core. DNA winds aroundthis protein core, with the basic amino acids of the histonesinteracting with the negatively charged phosphate groups of the DNA.Approximately 146 base pairs of DNA wrap around a histone core to makeup a nucleosome particle, the repeating structural motif of chromatin.

Csordas, Biochem. J., 286: 23-38 (1990) teaches that histones aresubject to posttranslational acetylation of the N-terminal lysineresidues, a reaction that is catalyzed by histone acetyl transferase(HAT1). Acetylation neutralizes the positive charge of the lysine sidechain, and is thought to impact chromatin structure. Indeed, Taunton etal., Science, 272: 408-411 (1996), teaches that access of transcriptionfactors to chromatin templates is enhanced by histone hyperacetylation.Taunton et al. further teaches that an enrichment in underacetylatedhistone H4 has been found in transcriptionally silent regions of thegenome.

Histone acetylation is a reversible modification, with deacetylationbeing catalyzed by a family of enzymes termed histone deacetylases(HDACs). The molecular cloning of gene sequences encoding proteins withHDAC activity has established the existence of a set of discrete HDACenzyme isoforms. Histone deacetylases play an important role in generegulation in mammalian cells. Gray and Ekstrom, Expr. Cell. Res. 262:75-83 (2001); Zhou et al., Proc. Natl. Acad. Sci. USA 98: 10572-10577(2001); Kao et al. J. Biol. Chem. 277: 187-193 (2002) and Gao et al. J.Biol. Chem. 277: 25748-25755 (2002) teach that there are 11 members ofthe histone deacetylase (HDAC) family.

Class I histone deacetylases include HDAC1, HDAC2, HDAC3 and HDAC8. TheClass I enzymes are expressed in a wide variety of tissues and arereported to be localized in the nucleus. Class II histone deacetylasesinclude HDAC4, HDAC5, HDAC6, HDAC7, HDAC9 and HDAC10. The Class IIenzymes have been described as limited in tissue distribution and theycan shuttle between the nucleus and the cytoplasm. The Class II enzymesare further divided into Class IIa (HDAC4, HDAC5, HDAC7 and HDAC9) andClass IIb (HDAC6 and HDAC10). Recent classifications place HDAC11 in aclass of its own.

Studies utilizing known HDAC inhibitors have established a link betweenacetylation and gene expression. Numerous studies have examined therelationship between HDAC and gene expression. Taunton et al., Science272:408-411 (1996), discloses a human HDAC that is related to a yeasttranscriptional regulator. Cress et al., J. Cell. Phys. 184:1-16 (2000),discloses that, in the context of human cancer, the role of HDAC is as acorepressor of transcription. Ng et al., TIBS 25: March (2000),discloses HDAC as a pervasive feature of transcriptional repressorsystems. Magnaghi-Jaulin et al., Prog. Cell Cycle Res. 4:41-47 (2000),discloses HDAC as a transcriptional co-regulator important for cellcycle progression.

Richon et al., Proc. Natl. Acad. Sci. USA, 95: 3003-3007 (1998),discloses that HDAC activity is inhibited by trichostatin A (TSA), anatural product isolated from Streptomyces hygroscopicus, which has beenshown to inhibit histone deacetylase activity and arrest cell cycleprogression in cells in the G1 and G2 phases (Yoshida et al., J. Biol.Chem. 265: 17174-17179, 1990; Yoshida et al., Exp. Cell Res. 177:122-131, 1988), and by a synthetic compound, suberoylanilide hydroxamicacid (SAHA). Yoshida and Beppu, Exper. Cell Res., 177: 122-131 (1988),teaches that TSA causes arrest of rat fibroblasts at the G₁ and G₂phases of the cell cycle, implicating HDAC in cell cycle regulation.Indeed, Finnin et al., Nature, 401: 188-193 (1999), teaches that TSA andSAHA inhibit cell growth, induce terminal differentiation, and preventthe formation of tumors in mice. Suzuki et al., U.S. Pat. No. 6,174,905,EP 0847992 and JP 258863/96, disclose benzamide derivatives that inducecell differentiation and inhibit HDAC. Delorme et al., WO 01/38322 andWO 2001/070675, disclose additional compounds that serve as HDACinhibitors. Other inhibitors of histone deacetylase activity, includingtrapoxin, depudecin, FR901228 (Fujisawa Pharmaceuticals), and butyrate,have been found to similarly inhibit cell cycle progression in cells(Taunton et al., Science 272: 408-411, 1996; Kijima et al., J. Biol.Chem. 268(30):22429-22435, 1993; Kwon et al., Proc. Natl. Acad. Sci. USA95(7):3356-61, 1998).

These and other findings suggest that inhibition of HDAC activityrepresents a novel approach for intervening in cell cycle regulation andthat HDAC inhibitors have great therapeutic potential in the studyand/or treatment of diseases or conditions ameliorated by modulatingHDAC activity. Inhibitors which are not selective for specific HDACisotype(s) may have undesirable side effects than an HDAC inhibitor thatis better able to target specific HDAC isoforms, and may thus be lessdesirable as an inhibitor or therapeutic agent. Identification ofinhibitors selective for specific HDAC isotype(s) will yield novelstrategies for understanding the role of histone deacetylases andtreating diseases ameliorated by modulating by HDAC activity.

SUMMARY OF THE INVENTION

The present invention provides compounds and methods for the inhibitionof HDAC enzymatic activity. The invention provides compounds and methodsfor treating diseases ameliorated by modulating by HDAC activity, suchas cell proliferative diseases and conditions.

In a first aspect, the present invention provides compounds that areuseful as inhibitors of HDAC and that have the Formula (I):

and N-oxides, hydrates, solvates, pharmaceutically acceptable salts,prodrugs and complexes thereof, and racemic and scalemic mixtures,diastereomers, tautomers and enantiomers thereof, wherein L, M, n, R, W,X and Y are as defined below. In this first aspect, the inventionprovides compounds of Formula I that are useful as HDAC inhibitors and,therefore, are useful research tools for the study of the role of HDACin both normal and disease states.

In a second aspect, the invention provides a composition comprising acompound according to the present invention. In one embodiment, thecomposition further comprises an additional inhibitory agent.

In a third aspect, the invention provides a method of inhibiting HDACactivity, in one embodiment HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9and/or HDAC11, the method comprising contacting the HDAC with a compoundaccording to the present invention, or with a composition according tothe present invention. Inhibition of HDAC can be in a cell or amulticellular organism. If in a cell, the method according to thisaspect of the invention comprises contacting the cell with a compoundaccording to the present invention, or with a composition according tothe present invention. If in a multicellular organism, the methodaccording to this aspect of the invention comprises administering to theorganism a compound according to the present invention, or a compositionaccording to the present invention. In one embodiment the organism is amammal, for example a human.

The present invention provides compounds for use in the manufacture of amedicament for the treatment of diseases ameliorated by modulating byHDAC activity.

The foregoing merely summarizes the above aspects of the invention andis not intended to be limiting in nature. These aspects and otheraspects and embodiments are described more fully below. The patent andscientific literature referred to herein establishes knowledge that isavailable to those with skill in the art. Each issued patent, patentapplication, and other publication cited herein is hereby incorporatedby reference in its entirety. In the case of inconsistencies, theteachings of the present disclosure will prevail.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides compounds and methods for the inhibitionof HDAC enzymatic activity. The invention also provides compounds andmethods for treating diseases ameliorated by modulating by HDACactivity, such as cell proliferative diseases and conditions.

In one aspect, the invention provides compounds of the Formula (I):

and N-oxides, hydrates, solvates, pharmaceutically acceptable salts,prodrugs and complexes thereof, and racemic and scalemic mixtures,diasteromers, tautomers and enantiomers thereof, wherein L, M, n, R, W,X and Y are as defined herein.

In the second aspect, the invention provides a composition comprising acompound according to the first aspect or any embodiment thereof and apharmaceutically acceptable carrier.

In a third aspect, the invention provides a method of inhibiting HDACactivity, the method comprising contacting the HDAC, or a cellcontaining HDAC activity with an inhibition effective amount of acompound according to the present invention, or with an inhibitioneffective amount of a composition according to the present inventionInhibition of HDAC activity can be in a cell or a multicellularorganism. If in a multicellular organism, the method according to thisaspect of the invention comprises administering to the organism aninhibition effective amount of a compound according to the presentinvention, or an inhibition effective amount of a composition accordingto the present invention. In one embodiment the organism is a mammal,for example a primate, such as a human. In one embodiment, the methodfurther comprises concurrently or sequentially contacting the HDAC, orthe cell, with an effective amount of an additional HDAC inhibitoryagent, or if in a multicellular organism, concurrently or sequentiallyadministering an inhibition effective amount of an additional HDACinhibitory agent.

In one embodiment of the third aspect, the method comprises inhibiting ahistone deacetylase selected from the group consisting of HDAC4, HDAC5,HDAC6, HDAC7, HDAC8, HDAC9 and/or HDAC11 in a cell comprising contactingthe cell with a histone deacetylase inhibiting amount of a compoundaccording to the present invention. In still another embodiment, themethod comprises inhibiting a histone deacetylase selected from thegroup consisting of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9 and/orHDAC11 in a cell comprising contacting the cell with a histonedeacetylase inhibiting amount of a composition according to the presentinvention. According to this aspect, the compounds and compositionsaccording to the invention are useful as tools for exploring the role ofhistone deacetylases, such as HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9and/or HDAC11, in various disease conditions. In other embodiments ofthis aspect, the histone deacetylase is selected from the groupconsisting of HDAC4, HDAC5, HDAC7 and HDAC9.

In some embodiments, the contacted cell is in an animal. Thus, theinvention provides a method for treating a disease ameliorated bymodulating by HDAC activity in an animal, comprising administering to ananimal in need of such treatment a therapeutically effective amount of acompound according to the present invention, or a pharmaceuticalcomposition thereof. In one embodiment, the animal is a mammal, forexample a domesticated mammal or a primate. In another embodiment, theanimal is a human.

In some embodiments the animal is administered an effective amount of acompound according to the present invention, or a pharmaceuticalcomposition thereof, in combination (simultaneously or sequentially)with at least one other anti-disease agent, or a composition thereof.The term “anti-disease agent” includes any agent that is useful for thetreatment of the particular disease for which treatment is desired.

For purposes of the present invention, the following definitions will beused (unless expressly stated otherwise).

Reference to “a compound of the formula (I), formula (II), etc.,” (orequivalently, “a compound according to the first aspect”, or “a compoundof the present invention”, and the like), herein is understood toinclude reference to N-oxides, hydrates, solvates, pharmaceuticallyacceptable salts, prodrugs and complexes thereof, and racemic andscalemic mixtures, diastereomers, enantiomers and tautomers thereof andunless otherwise indicated.

For simplicity, chemical moieties are defined and referred to throughoutprimarily as univalent chemical moieties (e.g., alkyl, aryl, etc.).Nevertheless, such terms are also used to convey correspondingmultivalent moieties under the appropriate structural circumstancesclear to those skilled in the art. For example, while an “alkyl” moietygenerally refers to a monovalent radical (e.g. CH₃—CH₂—), in certaincircumstances a bivalent linking moiety can be “alkyl,” in which casethose skilled in the art will understand the alkyl to be a divalentradical (e.g., —CH₂—CH₂—), which is equivalent to the term “alkylene.”(Similarly, in circumstances in which a divalent moiety is required andis stated as being “aryl,” those skilled in the art will understand thatthe term “aryl” refers to the corresponding divalent moiety, arylene).All atoms are understood to have their normal number of valences forbond formation (i.e., 4 for carbon, 3 for N, 2 for O, and 2, 4, or 6 forS, depending on the oxidation state of the S). On occasion a moiety maybe defined, for example, as (A)_(a)-B-, wherein a is 0 or 1. In suchinstances, when a is 0 the moiety is B- and when a is 1 the moiety isA-B-. Also, a number of moietes disclosed here may exist in multipletautomeric forms, all of which are intended to be encompassed by anygiven tautomeric structure.

For simplicity, reference to a “C_(n)-C_(m),” heterocyclyl or“C_(n)-C_(m)” heteroaryl means a heterocyclyl or heteroaryl having from“n” to “m” annular atoms, where “n” and “m” are integers. Thus, forexample, a C₅-C₆-heterocyclyl is a 5- or 6-membered ring having at leastone heteroatom, and includes, for example, pyrrolidinyl (C₅) andpiperidinyl (C₆); C₆-heteroaryl includes, for example, pyridyl andpyrimidyl.

The term “hydrocarbyl” refers to a straight, branched, or cyclic alkyl,alkenyl, or alkynyl, each as defined herein. A “C₀” hydrocarbyl is usedto refer to a covalent bond. Thus, “C₀-C₃-hydrocarbyl” includes acovalent bond, methyl, ethyl, ethenyl, ethynyl, propyl, propenyl,propynyl, and cyclopropyl.

The term “aliphatic” is intended to mean both saturated, partiallyunsaturated and unsaturated, straight chain or branched aliphatichydrocarbons. As will be appreciated by one of ordinary skill in theart, “aliphatic” is intended herein to include, but is not limited to,alkyl, alkenyl or alkynyl moieties.

The term “alkyl” is intended to mean a straight chain or branchedaliphatic group having from 1 to 12 carbon atoms, alternatively 1-8carbon atoms, and alternatively 1-6 carbon atoms. Other examples ofalkyl groups have from 2 to 12 carbon atoms, alternatively 2-8 carbonatoms and alternatively 2-6 carbon atoms. Examples of alkyl groupsinclude, without limitation, methyl, ethyl, propyl, isopropyl, butyl,isobutyl, sec-butyl, tert-butyl, pentyl, hexyl and the like. A “C₀”alkyl (as in “C₀-C₃alkyl”) is a covalent bond.

The term “alkenyl” is intended to mean an unsaturated or partiallyunsaturated straight chain or branched aliphatic group with one or morecarbon-carbon double bonds, having from 2 to 12 carbon atoms,alternatively 2-8 carbon atoms, and alternatively 2-6 carbon atoms.Examples of alkenyl groups include, without limitation, ethenyl,propenyl, butenyl, pentenyl, and hexenyl.

The term “alkynyl” is intended to mean an unsaturated or partiallyunsaturated straight chain or branched aliphatic group with one or morecarbon-carbon triple bonds, having from 2 to 12 carbon atoms,alternatively 2-8 carbon atoms, and alternatively 2-6 carbon atoms.Examples of alkynyl groups include, without limitation, ethynyl,propynyl, butynyl, pentynyl, and hexynyl.

The terms “alkylene,” “alkenylene,” or “alkynylene” as used herein areintended to mean an alkyl, alkenyl, or alkynyl group, respectively, asdefined hereinabove, that is positioned between and serves to connecttwo other chemical groups. Examples of alkylene groups include, withoutlimitation, methylene, ethylene, propylene, and butylene. Examples ofalkenylene groups include, without limitation, ethenylene, propenylene,and butenylene. Examples of alkynylene groups include, withoutlimitation, ethynylene, propynylene, and butynylene.

The term “azolyl” as employed herein is intended to mean a five-memberedsaturated or unsaturated heterocyclic group containing two or morehetero-atoms, as ring atoms, selected from the group consisting ofnitrogen, sulfur and oxygen, wherein at least one of the hetero-atoms isa nitrogen atom. Examples of azolyl groups include, but are not limitedto, optionally substituted imidazolyl, oxazolyl, thiazolyl, pyrazolyl,isoxazolyl, isothiazolyl, 1,3,4-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,4-o xadiazolyl, and 1,3,4-oxadiazolyl.

The term “carbocycle” as employed herein is intended to mean acycloalkyl or aryl moiety. The term “carbocycle” also includes acycloalkenyl moiety having at least one carbon-carbon double bond.

The term “cycloalkyl” is intended to mean a saturated, partiallyunsaturated or unsaturated mono-, bi-, tri- or poly-cyclic hydrocarbongroup having about 3 to 15 carbons, alternatively having 3 to 12carbons, alternatively 3 to 8 carbons, alternatively 3 to 6 carbons, andalternatively 5 or 6 carbons. In certain embodiments, the cycloalkylgroup is fused to an aryl, heteroaryl or heterocyclic group. Examples ofcycloalkyl groups include, without limitation, cyclopenten-2-enone,cyclopenten-2-enol, cyclohex-2-enone, cyclohex-2-enol, cyclopropyl,cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl,cyclohexenyl, cycloheptyl, cyclooctyl, etc.

The term “heteroalkyl” is intended to mean a saturated, partiallyunsaturated or unsaturated, straight chain or branched aliphatic group,wherein one or more carbon atoms in the group are independently replacedby a moiety selected from the group consisting of O, S, N, N-alkyl,—S(O)—, —S(O)₂—, —S(O)₂NH—, or —NHS(O)₂—.

The term “aryl” is intended to mean a mono-, bi-, tri- or polycyclicaromatic moiety, for example a C₆-C₁₄aromatic moiety, for examplecomprising one to three aromatic rings. Alternatively, the aryl group isa C₆-C₁₀aryl group, alternatively a C₆aryl group. Examples of arylgroups include, without limitation, phenyl, naphthyl, anthracenyl, andfluorenyl.

The terms “aralkyl” or “arylalkyl” are intended to mean a groupcomprising an aryl group covalently linked to an alkyl group. If anaralkyl group is described as “optionally substituted”, it is intendedthat either or both of the aryl and alkyl moieties may independently beoptionally substituted or unsubstituted. For example, the aralkyl groupis (C₁-C₆)alk(C₆-C₁₀)aryl, including, without limitation, benzyl,phenethyl, and naphthylmethyl. For simplicity, when written as“arylalkyl” this term, and terms related thereto, is intended toindicate the order of groups in a compound as “aryl-alkyl”. Similarly,“alkyl-aryl” is intended to indicate the order of the groups in acompound as “alkyl-aryl”.

The terms “heterocyclyl”, “heterocyclic” or “heterocycle” are intendedto mean a group which is a mono-, bi-, or polycyclic structure havingfrom about 3 to about 14 atoms, wherein one or more atoms areindependently selected from the group consisting of N, O, and S. Thering structure may be saturated, unsaturated or partially unsaturated.In certain embodiments, the heterocyclic group is non-aromatic, in whichcase the group is also known as a heterocycloalkyl. In certainembodiments, the heterocyclic group is a bridged heterocyclic group (forexample, a bicyclic moiety with a methylene, ethylene or propylenebridge). In a bicyclic or polycyclic structure, one or more rings may bearomatic; for example one ring of a bicyclic heterocycle or one or tworings of a tricyclic heterocycle may be aromatic, as in indan and9,10-dihydro anthracene. Examples of heterocyclic groups include,without limitation, epoxy, aziridinyl, tetrahydrofuranyl, pyrrolidinyl,piperidinyl, piperazinyl, thiazolidinyl, oxazolidinyl, oxazolidinonyl,and morpholino. In certain embodiments, the heterocyclic group is fusedto an aryl, heteroaryl, or cycloalkyl group. Examples of such fusedheterocycles include, without limitation, tetrahydroquinoline anddihydrobenzofuran. Specifically excluded from the scope of this term arecompounds where an annular O or S atom is adjacent to another O or Satom.

In certain embodiments, the heterocyclic group is a heteroaryl group. Asused herein, the term “heteroaryl” is intended to mean a mono-, bi-,tri- or polycyclic group having 5 to 18 ring atoms, alternatively 5 to14 ring atoms, alternatively 5, 6, 9, or 10 ring atoms; for examplehaving 6, 10, or 14 pi electrons shared in a cyclic array; and having,in addition to carbon atoms, between one or more heteroatoms selectedfrom the group consisting of N, O, and S. The term “heteroaryl” is alsointended to encompass the N-oxide derivative (or N-oxide derivatives, ifthe heteroaryl group contains more than one nitrogen such that more thanone N-oxide derivative may be formed) of a nitrogen-containingheteroaryl group. For example, a heteroaryl group may be pyrimidinyl,pyridinyl, benzimidazolyl, thienyl, benzothiazolyl, benzofuranyl andindolinyl. Examples of heteroaryl groups include, without limitation,thienyl, benzothienyl, furyl, benzofuryl, dibenzofuryl, pyrrolyl,imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, indolyl,quinolyl, isoquinolyl, quinoxalinyl, tetrazolyl, oxazolyl, thiazolyl,isoxazolyl, benzo[b]thienyl, naphtha[2,3-b]thianthrenyl, zanthenyl,quinolyl, benzothiazolyl, benzimidazolyl, beta-carbolinyl andperimidinyl. Illustrative examples of N-oxide derivatives of heteroarylgroups include, but are not limited to, pyridyl N-oxide, pyrazinylN-opxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, triazinyl N-oxide,isoquinolyl N-oxide and quinolyl N-oxide.

The terms “arylene,” “heteroarylene,” or “heterocyclylene” are intendedto mean an aryl, heteroaryl, or heterocyclyl group, respectively, asdefined hereinabove, that is positioned between and serves to connecttwo other chemical groups.

A heteroalicyclic group refers specifically to a non-aromaticheterocyclyl radical. A heteroalicyclic may contain unsaturation, but isnot aromatic.

A heterocyclylalkyl group refers to a residue in which a heterocyclyl isattached to a parent structure via one of an alkylene, alkylidene, oralkylidyne radical. Examples include (4-methylpiperazin-1-yl) methyl,(morpholin-4-yl) methyl, (pyridine-4-yl)methyl,2-(oxazolin-2-yl)ethyl,4-(4-methylpiperazin-1-yl)-2-butenyl, andthe like. If a heterocyclylalkyl is described as “optionallysubstituted” it is meant that both the heterocyclyl and thecorresponding alkylene, alkylidene, or alkylidyne radical portion of aheterocyclylalkyl group may be optionally substituted. A “lowerheterocyclylalkyl” refers to a heterocyclylalkyl where the “alkyl”portion of the group has one to six carbons.

A heteroalicyclylalkyl group refers specifically to a heterocyclylalkylwhere the heterocyclyl portion of the group is non-aromatic.

Other examples of heterocyclyls and heteroaryls include, but are notlimited to, azepinyl, azetidinyl, acridinyl, azocinyl, benzidolyl,benzimidazolyl, benzofuranyl, benzofurazanyl, benzofuryl,benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzothiazolyl,benzothienyl, benztriazolyl, benztetrazolyl, benzisoxazolyl,benzisothiazolyl, benzimidazolinyl, benzoxazolyl, benzoxadiazolyl,benzopyranyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl,chromenyl, cinnolinyl, coumarinyl, decahydroquinolinyl, dibenzofuryl,1,3-dioxolane, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, dihydroisoindolyl,dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), furanyl,furopyridinyl (such as fuor[2,3-c]pyridinyl, furo[3,2-b]pyridinyl orfuro[2,3-b]pyridinyl), furyl, furazanyl, hexahydrodiazepinyl,imidazolidinyl, imidazolinyl, imidazolyl, indazolyl, 1H-indazolyl,indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl,isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolyl,isoquinolinyl, isothiazolidinyl, isothiazolyl, isoxazolinyl, isoxazolyl,methylenedioxyphenyl, morpholinyl, naphthyridinyl,octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl,oxazolyl, oxazolidinyl, oxetanyl, 2-oxoazepinyl, 2-oxopiperazinyl,2-oxopiperidinyl, 2-oxopyrrolodinyl, pyrimidinyl, phenanthridinyl,phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl,phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl,4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl,pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole,pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl,pyrrolidinyl, pyrrolinyl, pyrrolopyridyl, 2H-pyrrolyl, pyrrolyl,quinazolinyl, quinolyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl,quinuclidinyl, tetrahydro-1,1-dioxothienyl, tetrahydrofuranyl,tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydroquinolinyl,tetrahydropyranyl, tetrazolyl, thiazolidinyl, 6H-1,2,5-thiadiazinyl,thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl), thiamorpholinyl,thiamorpholinyl sulfoxide, thiamorpholuiyl sulfone, thianthrenyl,thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thiophenyl, triazinyl, triazinylazepinyl, triazolyl (e.g.,1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl), andxanthenyl.

A “halohydrocarbyl” as employed herein is a hydrocarbyl moiety, in whichfrom one to all hydrogens have been replaced with an independentlyselected halo.

Aromatic polycycles include, but are not limited to, bicyclic andtricyclic fused ring systems, including for example naphthyl andquinoline.

Non-aromatic polycycles include, but are not limited to, bicyclic andtricyclic fused ring systems where each ring is independently 4-9membered and each ring independently contains zero, one or more doubleand/or triple bonds. Suitable examples of non-aromatic polycyclesinclude, but are not limited to, decalin, octahydroindene,perhydrobenzocycloheptene and perhydrobenzo-[f]azulene.

Polyheteroaryl groups include bicyclic and tricyclic fused rings systemswhere each ring is independently be 5 or 6 membered and independentlycontain one or more heteroatom, for example, 1, 2, 3 or 4 heteroatoms,independently chosen from O, N and S such that the fused ring system isaromatic. Suitable examples of polyheteroaryl ring systems includequinoline, isoquinoline, pyridopyrazine, pyrrolopyridine, furopyridine,indole, benzofuran, benzothiofuran, benzindole, benzoxazole,pyrroloquinoline, and the like.

Non-aromatic polyheterocyclic groups include but are not limited tobicyclic and tricyclic ring systems where each ring is independently 4-9membered, independently contains one or more heteroatom, for example 1,2, 3 or 4 heteroatoms, independently chosen from O, N and S, andindependently contains zero, or one or more C—C double or triple bonds.Suitable examples of non-aromatic polyheterocycles include but are notlimited to, hexitol, cis-perhydro-cyclohepta[b]pyridinyl,decahydro-benzo[f][1,4]oxazepinyl, 2,8-dioxabicyclo[3.3.0]octane,hexahydro-thieno[3,2-b]thiophene, perhydropyrrolo[3,2-b]pyrrole,perhydronaphthyridine, perhydrop-1H-dicyclopenta[b,e]pyran.

Mixed aryl and non-aryl polyheterocycle groups include but are notlimited to bicyclic and tricyclic fused ring systems where each ring isindependently 4-9 membered, and at least one ring contains one or moreheteroatom independently chosen from O, N and S, and at least one of therings must be aromatic. Suitable examples of mixed aryl and non-arylpolyheteorcycles include 2,3-dihydroindole, 1,2,3,4-tetrahydroquinoline,5,11-dihydro-10H-dibenz[b,e][1,4]diazepine,5H-dibenzo[b,e][1,4]diazepine,1,2-dihydropyrrolo[3,4-b][1,5]benzodiazepine,1,5-dihydropyrido[2,3-b][1,4]diazepin-4-one,1,2,3,4,6,11-hexhydro-benzo[b]pyrido[2,3-e][1,4]diazepine-5-one,methylenedioxyphenyl, bis-methylenedioxyphenyl,1,2,3,4-tetrahydronaphthalene, dibenzosuberane dihydroanthracene and9H-fluorene.

As employed herein, and unless stated otherwise, when a moiety (e.g.,alkyl, heteroalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, etc.) isdescribed as “optionally substituted” it is meant that the groupoptionally has from one to four, alternatively from one to three,alternatively one or two, independently selected non-hydrogensubstituents. Suitable substituents include, without limitation, halo,hydroxy, oxo (e.g., an annular —CH— substituted with oxo is —C(O)—)nitro, halohydrocarbyl, hydrocarbyl, alkyl, cycloalkyl, heterocyclyl,heteroaryl, aralkyl, alkoxy, aryloxy, amino, acylamino, alkylcarbamoyl,arylcarbamoyl, aminoalkyl, acyl, carboxy, hydroxyalkyl, alkanesulfonyl,arenesulfonyl, alkanesulfonamido, arenesulfonamido, aralkylsulfonamido,alkylcarbonyl, acyloxy, cyano, and ureido groups. Examples ofsubstituents, which are themselves not further substituted (unlessexpressly stated otherwise) are:

-   -   (a) halo, hydroxy, cyano, oxo, carboxy, formyl, nitro, amino,        amidino, guanidino,    -   (b) C₁-C₅alkyl or alkenyl or arylalkyl imino, carbamoyl, azido,        carboxamido, mercapto, hydroxy, hydroxyalkyl, alkylaryl,        arylalkyl, C₁-C₈alkenyl, C₁-C₈alkoxy, C₁-C₈alkyamino,        C₁-C₈alkoxycarbonyl, aryloxycarbonyl, C₂-C₈acyl,        —C(O)—N(R³⁰)-alkyl-cycloalkyl, —C(O)—N(R³⁰)—alkyl-heterocyclyl,        —C(O)—N(R³⁰)-alkyl-aryl, —C(O)—N(R³⁰)-alkyl-heteroaryl,        —C(O)-cycloalkyl, —C(O)-heterocyclyl, —C(O)-aryl, —C(O)-hetero        aryl, C₂-C₈acylamino, C₁-C₈alkylthio, arylalkylthio, arylthio,        C₁-C₈alkylsulfinyl, arylalkylsulfinyl, arylsulfinyl,        C₁-C₈alkylsulfonyl, arylalkylsulfonyl, arylsulfonyl,        C₀-C₆N-alkyl carbamoyl, C₂-C₁₅N,N-dialkylcarbamoyl, C₃-C₇        cycloalkyl, aroyl, aryloxy, arylalkyl ether, aryl, aryl fused to        a cycloalkyl or heterocycle or another awl ring,        C₃-C₇heterocycle, C₅-C₁₅heteroaryl or any of these rings fused        or spiro-fused to a cycloalkyl, heterocyclyl, or aryl, wherein        each of the foregoing is further optionally substituted with one        more moieties listed in (a), above; and    -   (c) —(CR³²R³³)_(s)—NR³⁰R³¹, wherein s is from 0 (in which case        the nitrogen is directly bonded to the moiety that is        substituted) to 6, R³² and R³³ are each independently hydrogen,        halo, hydroxyl or C₁-C₄alkyl, and R³⁰ and R³¹ are each        independently hydrogen, cyano, oxo, hydroxyl, C₁-C₈alkyl,        C₁-C₈hetero alkyl, C₁-C₈alkenyl, carboxamido,        C₁-C₃alkyl-carboxamido, carboxamido-C₁-C₃alkyl, amidino,        C₂-C₈hydroxyalkyl, C₁-C₃alkylaryl, aryl-C₁-C₃alkyl,        C₁-C₃alkylheteroaryl, heteroaryl-C₁-C₃alkyl,        C₁-C₃alkylheterocyclyl, heterocyclyl-C₁-C₃alkyl        C₁-C₃alkylcycloalkyl, cycloalkyl-C₁-C₃ alkyl, C₂-C₈ alkoxy,        C₂-C₈alkoxy-C₁-C₄alkyl, C₁-C₈alkoxycarbonyl, aryloxycarbonyl,        aryl-C₁-C₃alkoxycarbonyl, heteroaryloxycarbonyl,        heteroaryl-C₁-C₃alkoxycarbonyl, C₁-C₈acyl, C₀-C₈alkyl-carbonyl,        aryl-C₀-C₈alkyl-carbonyl, heteroaryl-C₀-C₈alkyl-carbonyl,        cycloalkyl-C₀-C₈alkyl-carbonyl,        heterocyclyl-C₀-C₈alkyl-carbonyl, C₀-C₈alkyl-NH-carbonyl,        aryl-C₀-C₈alkyl-NH-carbonyl, heteroaryl-C₀-C₈alkyl-NH-carbonyl,        cycloalkyl-C₀-C₈alkyl-NH-carbonyl,        heterocyclyl-C₀-C₈alkyl-NH-carbonyl, cycloalkyl-S(O)₂—,        heterocyclyl-S(O)₂—, aryl-S(O)₂—, heteroaryl-S(O)₂—,        C₀-C₈alkyl-O-carbonyl, aryl-C₀-C₈alkyl-O-carbonyl,        heteroaryl-C₀-C₈alkyl-O-carbonyl,        cycloalkyl-C₀-C₈alkyl-O-carbonyl,        heterocyclyl-C₀-C₈alkyl-O-carbonyl, C₁-C₈alkylsulfonyl,        arylalkylsulfonyl, arylsulfonyl, heteroarylalkylsulfonyl,        heteroarylsulfonyl, C₁-C₈ alkyl-NH-sulfonyl,        arylalkyl-NH-sulfonyl, aryl-NH-sulfonyl,        heteroarylalkyl-NH-sulfonyl, heteroaryl-NH-sulfonyl aroyl, aryl,        cycloalkyl, heterocyclyl, heteroaryl, aryl-C₁-C₃alkyl-,        cycloalkyl-C₁-C₃alkyl-, heterocyclyl-C₁-C₃alkyl-,        heteroaryl-C₁-C₃alkyl-, or a protecting group, wherein each of        the foregoing is further optionally substituted with one more        moieties listed in (a), above; or    -   R³⁰ and R³¹ taken together with the N to which they are attached        form a heterocyclyl or heteroaryl, each of which is optionally        substituted with from 1 to 3 substituents selected from the        group consisting of (a) above, a protecting group, and        (X³⁰—Y³¹—), wherein said heterocyclyl may also be bridged        (forming a bicyclic moiety with a methylene, ethylene or        propylene bridge); wherein    -   X³⁰ is selected from the group consisting of H, C₁-C₈alkyl,        C₂-C₈alkenyl-, C₂-C₈alkynyl-,        —C₀-C₃alkyl-C₂-C₈alkenyl-C₀-C₃alkyl,        C₀-C₃alkyl-C₂-C₈alkynyl-C₀-C₃alkyl, C₀-C₃alkyl-O—C₀-C₃alkyl-,        HO—C₀-C₃alkyl-, C₀-C₄alkyl-N(R³⁰)—C₀-C₃alkyl-,        N(R³⁰)(R³¹)—C₀-C₃alkyl-, N(R³⁰)(R³¹)—C₀-C₃alkenyl-,        N(R³⁰)(R³¹)—C₀-C₃alkynyl-, (N(R³⁰)(R³¹))₂—C═N—,        C₀-C₃alkyl-S(O)₀₋₂—C₀-C₃alkyl-, CF₃—C₀-C₃alkyl-,        C₁-C₈heteroalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl,        aryl-C₁-C₃ alkyl-, cycloalkyl-C₁-C₃alkyl-,        heterocyclyl-C₁-C₃alkyl-, heteroaryl-C₁-C₃alkyl-,        N(R³⁰)(R³¹)-heterocyclyl-C₁-C₃alkyl-, wherein the aryl,        cycloalkyl, heteroaryl and heterocycyl are optionally        substituted with from 1 to 3 substituents from (a); and    -   Y³¹ is selected from the group consisting of a direct bond, —O—,        —N(R³⁰)—, —C(O)—, —O—C(O)—, —C(O)—O—, —N(R³⁰)—C(O)—,        —C(O)—N(R³⁰)—, —N(R³⁰)—C(S)—, —C(S)—N(R³⁰)—,        —N(R³⁰)—C(O)—N(R³¹)—, —N(R³⁰)—C(NR³⁰)—N(R³¹)—, —N(R³⁰)—C(NR³¹)—,        —C(NR³¹)—N(R³⁰)—, —N(R³⁰)—C(S)—N(R³¹)—, —N(R³⁰)—C(O)—O—,        —O—C(O)—N(R³¹)—, —N(R³⁰)—C(S)—O—, —O—C(S)—N(R³¹)—, —S(O)₀₋₂—,        —SO₂N(R³¹)—, —N(R³¹)—SO₂— and —N(R³⁰)—SO₂N(R³¹)—.

A moiety that is substituted is one in which one or more (for exampleone to four, alternatively from one to three and alternatively one ortwo), hydrogens have been independently replaced with another chemicalsubstituent. As a non-limiting example, substituted phenyls include2-fluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-fluoro-phenyl,2-fluoro-3-propylphenyl. As another non-limiting example, substitutedn-octyls include 2,4-dimethyl-5-ethyl-octyl and 3-cyclopentyl-octyl.Included within this definition are methylenes (—CH₂—) substituted withoxygen to form carbonyl —CO—.

When there are two optional substituents bonded to adjacent atoms of aring structure, such as for example a phenyl, thiophenyl, or pyridinyl,the substituents, together with the atoms to which they are bonded,optionally form a 5- or 6-membered cycloalkyl or heterocycle having 1,2, or 3 annular heteroatoms.

In certain embodiments, a group, such as a hydrocarbyl, heteroalkyl,heterocyclic and/or aryl group is unsubstituted.

In other embodiments, a group, such as a hydrocarbyl, heteroalkyl,heterocyclic and/or aryl group is substituted with from 1 to 4(alternatively from one to three, and alternatively one or two)independently selected substituents.

Examples of substituents on alkyl groups include, but are not limitedto, hydroxyl, halogen (e.g., a single halogen substituent or multiplehalo substituents; in the latter case, groups such as —CF₃ or an alkylgroup bearing Cl₃), oxo, cyano, nitro, alkyl, cycloalkyl, alkenyl,cycloalkenyl, alkynyl, heterocycle, aryl, —OR^(a1), —SR^(a1),—S(═O)R^(e1), —S(═O)₂R^(e1), —P(═O)₂R^(e1), —S(═O)₂OR^(e1),—P(═O)₂OR^(e1), —NR^(b1)R^(c1), —NR^(b1)S(═O)₂R^(e1),—NR^(b1)P(═O)₂R^(e1), —S(═O)₂NR^(b1)R^(c1), —P(═O)₂NR^(b1)R^(c1),—C(═O)OR^(e1), —C(═O)R^(a1), —C(═O)NR^(b1)R^(c1), —OC(═O)R^(a1),—OC(═O)NR^(b1)R^(c1), —NR^(b1)C(═O)OR^(e1), —NR^(d1)C(═O)NR^(b1)R^(c1),—NR^(d1)S(═O)₂NR^(b1)R^(c1), —NR^(d1)P(═O)₂NR^(b1)R^(c1),—NR^(b1)C(═O)R^(a1) or —NR^(b1)P(═O)₂R^(e1), wherein R^(a1) is hydrogen,alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle or aryl;R^(b1), R^(c1) and R^(d1) are independently hydrogen, alkyl, cycloalkyl,heterocycle or aryl, or said R^(b1) and R^(c1) together with the N towhich they are bonded optionally form a heterocycle; and R^(e1) isalkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle or aryl.In the aforementioned exemplary substituents, groups such as alkyl,cycloalkyl, alkenyl, alkynyl, cycloalkenyl, heterocycle and aryl canthemselves be optionally substituted.

Examples of substituents on alkenyl and alkynyl groups include, but arenot limited to, alkyl or substituted alkyl, as well as those groupsrecited as examples of alkyl substituents.

Examples of substituents on cycloalkyl groups include, but are notlimited to, nitro, cyano, alkyl or substituted alkyl, as well as thosegroups recited about as examples of alkyl substituents. Other examplesof substituents include, but are not limited to, spiro-attached or fusedcyclic substituents, for example spiro-attached cycloalkyl,spiro-attached cycloalkenyl, spiro-attached heterocycle (excludingheteroaryl), fused cycloalkyl, fused cycloalkenyl, fused heterocycle, orfused aryl, where the aforementioned cycloalkyl, cycloalkenyl,heterocycle and aryl substituents can themselves be optionallysubstituted. In certain embodiments, when a cycloalkyl is substituted bytwo C₁₋₆ alkyl groups, the two alkyl groups may combine together to forman alkylene chain, for example a C₁₋₃ alkylene chain. Cycloalkyl groupshaving this crosslinked structure include bicyclo[2.2.2]octanyl andnorbornanyl.

Examples of substituents on cycloalkenyl groups include, but are notlimited to, nitro, cyano, alkyl or substituted alkyl, as well as thosegroups recited as examples of alkyl substituents. Other examples ofsubstituents include, but are not limited to, spiro-attached or fusedcyclic substituents, especially spiro-attached cycloalkyl,spiro-attached cycloalkenyl, spiro-attached heterocycle (excludingheteroaryl), fused cycloalkyl, fused cycloalkenyl, fused heterocycle, orfused aryl, where the aforementioned cycloalkyl, cycloalkenyl,heterocycle and aryl substituents can themselves be optionallysubstituted. In certain embodiments, when a cycloalkenyl is substitutedby two C₁₋₆ alkyl groups, the two alkyl groups may combine together toform an alkylene chain, for example a C₁₋₃ alkylene chain.

Examples of substituents on aryl groups include, but are not limited to,nitro, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substitutedcycloalkenyl, cyano, alkyl or substituted alkyl, as well as those groupsrecited above as examples of alkyl substituents. Other examples ofsubstituents include, but are not limited to, fused cyclic groups,especially fused cycloalkyl, fused cycloalkenyl, fused heterocycle, orfused aryl, where the aforementioned cycloalkyl, cylcoalkenyl,heterocycle and aryl substituents can themselves be optionallysubstituted. Still other substituents on aryl groups (phenyl, as anon-limiting example) include, but are not limited to, haloalkyl andthose groups recited as examples of alkyl substituents. In certainembodiments, when an aryl group is substituted by two C₁₋₆ alkyl groups,the two alkyl groups may combine together to form an alkylene chain, forexample a C₁₋₃ alkylene chain.

Examples of substituents on heterocyclic groups include, but are notlimited to, cycloalkyl, substituted cycloalkyl, cycloalkenyl,substituted cycloalkenyl, nitro, oxo (i.e., ═O), cyano, alkyl,substituted alkyl, as well as those groups recited as examples of alkylsubstituents. Other substituents on heterocyclic groups include, but arenot limited to, spiro-attached or fused cylic substituents at anyavailable point or points of attachment, for example spiro-attachedcycloalkyl, spiro-attached cycloalkenyl, spiro-attached heterocycle(excluding heteroaryl), fused cycloalkyl, fused cycloakenyl, fusedheterocycle and fused aryl, where the aforementioned cycloalkyl,cycloalkenyl, heterocycle and aryl substituents can themselves beoptionally substituted. In certain embodiments, when a heterocyclic issubstituted by two C₁₋₆ alkyl groups, the two alkyl groups may combinetogether to form an alkylene chain, for example a C₁₋₃ alkylene chain.

In certain embodiments, a heterocyclic group is substituted on carbon,nitrogen and/or sulfur at one or more positions. Examples ofsubstituents on carbon include those groups recited as examples of alkylsubstituents. Examples of substituents on nitrogen include, but are notlimited to alkyl, aryl, aralkyl, alkylcarbonyl, alkylsulfonyl,arylcarbonyl, arylsulfonyl, alkoxycarbonyl, or aralkoxycarbonyl.Examples of substituents on sulfur include, but are not limited to, oxoand C₁₋₆alkyl. In certain embodiments, nitrogen and sulfur heteroatomsmay independently be optionally oxidized and nitrogen heteroatoms mayindependently be optionally quaternized.

In certain embodiments, substituents on ring groups, such as aryl,heteroaryl, cycloalkyl and heterocyclyl, are selected from halogen,alkoxy and alkyl.

In certain embodiments, substituents on alkyl groups are selected fromhalogen and hydroxy.

Examples of substituents on aromatic polycycles include, but are notlimited to, C₁-C₆alkyl, cycloalkylalkyl (e.g. cyclopropylmethyl),oxyalkyl, halo, nitro, amino, alkylamino, aminoalkyl, alkyl ketones,nitrile, carboxyalkyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl andOR^(aa), such as alkoxy, wherein R^(aa) is selected from the groupconsisting of H, C₁-C₆alkyl, C₄-C₉cycloalkyl, C₄-C₉heterocycloalkyl,aryl, heteroaryl, arylalkyl, heteroarylalkyl and (CH₂)₀₋₆Z^(a)R^(bb),wherein Z^(a) is selected from the group consisting of O, NR^(cc), S andS(O), and R^(bb) is selected from the group consisting of H, C₁-C₆alkyl,C₄-C₉cycloalkyl, C₄-C₉heterocycloalkyl, C₄-C₉heterocycloalkylalkyl,aryl, mixed aryl and non-aryl polycycle, heteroaryl, arylalkyl, (e.g.benzyl), and heteroarylalkyl (e.g. pyridylmethyl); and R^(cc) isselected from the group consisting of H, C₁-C₆alkyl, C₄-C₉cycloalkyl,C₄-C₉heterocycloalkyl, aryl, heteroaryl, arylalkyl (e.g. benzyl),heteroarylalkyl (e.g. pyridylmethyl) and amino acyl.

Examples of substituents on non-aromatic polycycles include, but are notlimited to, oxo, C₃-C₉cycloalkyl, such as cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl and the like. Unless otherwise noted,non-aromatic polycycle substituents include both unsubstitutedcycloalkyl groups and cycloalkyl groups that are substituted by one ormore suitable substituents, including but not limited to, C₁-C₆alkyl,oxo, halo, hydroxy, aminoalkyl, oxyalkyl, alkylamino and OR^(aa), suchas alkoxy. In certain embodiments, substituents for such cycloalkylgroups include halo, hydroxy, alkoxy, oxyalkyl, alkylamino andaminoalkyl.

Examples of substituents on carbon atoms of polyheteroaryl groupsinclude but are not limited to, straight and branched optionallysubstituted C₁-C₆alkyl, unsaturation (i.e., there are one or more doubleor triple C—C bonds), acyl, oxo, cycloalkyl, halo, oxyalkyl, alkylamino,aminoalkyl, acylamino, OR^(aa) (for example alkoxy), and a substituentof the formula —O—(CH₂CH═CH(CH₃)(CH₂))₁₋₃H. Examples of suitablestraight and branched C₁-C₆alkyl substituents include but are notlimited to methyl, ethyl, n-propyl, 2-propyl, n-butyl, sec-butyl,t-butyl and the like. In certain embodiments, substituents are selectedfrom halo, hydroxy, alkoxy, oxyalkyl, alkylamino and aminoalkyl.Examples of substitutions on nitrogen atoms include, for example N-oxideor R^(cc). In certain embodiments, examples of substituents on nitrogenatoms include H, C₁-C₄alkyl, acyl, aminoacyl and sulfonyl. In certainembodiments, sulfur atoms are unsubstituted. Examples of substituents onsulfur atoms include but are not limited to oxo and lower alkyl.

Examples of substituents on carbon atoms of non-aromaticpolyheterocyclic groups include but are not limited to straight andbranched optionally substituted C₁-C₆alkyl, unsaturation (i.e., thereare one or more double or triple C—C bonds), acyl, oxo, cycloalkyl,halo, oxyalkyl, alkylamino, aminoalkyl, acylamino and OR^(aa), forexample alkoxy. Examples of suitable straight and branched C₁-C₆alkylsubstituents include but are not limited to methyl, ethyl, n-propyl,2-propyl, n-butyl, sec-butyl, t-butyl and the like. In certainembodiments, substituents are selected from halo, hydroxy, alkoxy,oxyalkyl, alkylamino and aminoalkyl. Examples of substitutions onnitrogen atoms include, for example, N-oxide or R^(cc). In certainembodiments, examples of N substituents include H, C₁-C₄ alkyl, acyl,aminoacyl and sulfonyl. In certain embodiments sulfur atoms areunsubstituted. Examples of S substituents include oxo and lower alkyl.

Examples of substituents on mixed aryl and non-aryl polyheterocyclegroups include, but are not limited to, nitro or as described above fornon-aromatic polycycle groups. In certain embodiments, substituents oncarbon atoms include, but are not limited to, —N—OH, ═N—OH, optionallysubstituted alkyl, unsaturation (i.e., there are one or more double ortriple C—C bonds), oxo, acyl, cycloalkyl, halo, oxyalkyl, alkylamino,aminoalkyl, acylamino and OR^(aa), for example alkoxy. In certainembodiments, substitutions on nitrogen atoms include, for example,N-oxide or R^(cc). In other embodiments, examples of N substituentsinclude H, C₁₋₄alkyl, acyl aminoacyl and sulfonyl. In certainembodiments, sulfur atoms are unsubstituted. Examples of S substituentsinclude oxo and lower alkyl.

The term “halogen” or “halo” as employed herein refers to chlorine,bromine, fluorine, or iodine. As herein employed, the term “acyl” refersto an alkylcarbonyl or arylcarbonyl substituent. The term “acylamino”refers to an amide group attached at the nitrogen atom (i.e., R—CO—NH—).The term “carbamoyl” refers to an amide group attached at the carbonylcarbon atom (i.e., NH₂—CO—). The nitrogen atom of an acylamino orcarbamoyl substituent is additionally optionally substituted. The term“sulfonamido” refers to a sulfonamide substituent attached by either thesulfur or the nitrogen atom. The term “amino” is meant to include NH₂,alkylamino, di-alkyl-amino, arylamino, and cyclic amino groups. The term“ureido” as employed herein refers to a substituted or unsubstitutedurea moiety.

The term “radical” as used herein means a chemical moiety comprising oneor more unpaired electrons.

Where optional substituents of a moiety are chosen from “one or more”groups it is to be understood that the moiety optionally has, unlessotherwise stated, from one up to the maximum number of substitutablehydrogens on the moiety replaced with a substituent independently chosenfrom among the specified groups.

In addition, substituents on cyclic moieties (i.e., cycloalkyl,heterocyclyl, aryl, heteroaryl) include 5- to 6-membered mono- and 9- to14-membered bi-cyclic moieties fused to the parent cyclic moiety to forma bi- or tri-cyclic fused ring system. Substituents on cyclic moietiesalso include 5- to 6-membered mono- and 9- to 14-membered bi-cyclicmoieties attached to the parent cyclic moiety by a covalent bond to forma bi- or tri-cyclic bi-ring system. For example, an optionallysubstituted phenyl includes, but is not limited to, the following:

A saturated, unsaturated or partially unsaturated three- toeight-membered carbocyclic ring is for example a four- toseven-membered, alternatively a five- or six-membered, saturated,unsaturated or partially unsaturated carbocyclic ring. Examples ofsaturated, unsaturated or partially unsaturated three- to eight-memberedcarbocyclic rings include phenyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, and cycloheptyl.

A saturated, unsaturated or partially unsaturated three- toeight-membered heterocyclic ring contains at least one heteroatomselected from oxygen, nitrogen, and sulfur atoms. For example, asaturated, unsaturated or partially unsaturated three- to eight-memberedheterocyclic ring can contain one or two heteroatoms with the remainingring-constituting atoms being carbon atoms. The saturated, unsaturatedor partially unsaturated three- to eight-membered heterocyclic ring isfor example a saturated, unsaturated or partially unsaturated four- toseven-membered heterocyclic ring, alternatively a saturated, unsaturatedor partially unsaturated five- or six-membered heterocyclic ring.Examples of saturated, unsaturated or partially unsaturated three- toeight-membered heterocyclic groups include thienyl, pyridyl,1,2,3-triazolyl, imidazolyl, isoxazolyl, pyrazolyl, piperazinyl,piperazino, piperidyl, piperidino, morpholinyl, morpholino,homopiperazinyl, homopiperazino, thiomorpholinyl, thiomorpholino,tetrahydropyrrolyl, and azepanyl.

The terms “inhibition effective amount” or “histone deacetylaseinhibiting amount” are meant to denote a dosage or amount sufficient tocause inhibition of histone deacetylase activity in vitro or in vivo.The histone deacetylase may be in a cell, which cell can be in amulticellular organism. The multicellular organism can be a plant orfungus, or an animal, for example a mammal, for example a human. Thefungus may be infecting a plant or a mammal, for example a human, andcould therefore be located in and/or on the plant or mammal. If thehistone deacetylase is in a multicellular organism, the method accordingto this aspect of the invention comprises administering to the organisma compound or composition according to the present invention.Administration may be by any route, including, without limitation,parenteral, oral, sublingual, transdermal, topical, intranasal,intratracheal, or intrarectal. In certain embodiments, compounds of theinvention are administered intravenously in a hospital setting. Incertain other embodiments, administration may be by the oral route.

In certain embodiments, HDAC inhibition is specific, i.e., the HDACinhibitor reduces a functional property or biological ability of a HDACat a concentration that is lower than the concentration of the inhibitorthat is required to produce another, unrelated biological effect. Forexample, the concentration of the inhibitor required for HDAC inhibitoryactivity is at least 2-fold lower, alternatively at least 5-fold lower,alternatively at least 10-fold lower, and alternatively at least 20-foldlower than the concentration required to produce an unrelated biologicaleffect.

The term “therapeutically effective amount” as employed herein is anamount of a compound of the invention, that when administered to apatient, treats a disease. The amount of a compound of the inventionwhich constitutes a “therapeutically effective amount” will varydepending on the compound, the disease, the disease state and itsseverity, the age, sex, health, size of the patient to be treated, theresults desired, and the like. The therapeutically effective amount canbe determined routinely by one of ordinary skill in the art. Optimalamounts can be determined based on monitoring of the patient's responseto treatment.

The term “patient” as employed herein for the purposes of the presentinvention includes humans and other animals, for example mammals, andother organisms. Thus the compounds, compositions and methods of thepresent invention are applicable for example to both human therapy andveterinary applications. In one embodiment the patient is a mammal, forexample a human.

The terms “treating”, “treatment”, or the like, as used herein coversthe treatment of a disease-state in an organism and includes at leastone of (i) preventing the disease-state from occurring, in particular,when such organism is predisposed to the disease-state but has not yetbeen diagnosed as having it; (ii) inhibiting the disease-state, i.e.,partially or completely arresting its development; (iii) relieving thedisease-state, i.e., causing regression of symptoms of thedisease-state, or ameliorating a symptom of the disease; and (iv)reversal or regression of the disease-state, for example eliminating orcuring of the disease. In certain embodiments of the present inventionthe organism is a mammal, for example a primate, for example a human. Asis known in the art, adjustments for systemic versus localized delivery,age, body weight, general health, sex, diet, time of administration,drug interaction and the severity of the condition may be necessary, andwill be ascertainable with routine experimentation by one of ordinaryskill in the art. In certain embodiments, the terms “treating”,“treatment”, or the like, as used herein covers the treatment of adisease-state in an organism and includes at least one of (ii), (iii)and (iv) above.

As used herein, the terms “histone deacetylase” and “HDAC” are intendedto refer to any one of a family of enzymes that remove acetyl groupsfrom a protein (for example, a histone, or tubulin). Unless otherwiseindicated by context, the term “histone” is meant to refer to anyhistone protein, including H1, H2A, H2B, H3, H4, and H5, from anyspecies. Examples of histone deacetylases include class II enzymes. Forexample the histone deacetylase is a human HDAC, including, but notlimited to, HDAC-4, HDAC-5, HDAC-6, HDAC-7, HDAC-8, HDAC-9 and HDAC-10.In some other embodiments, the histone deacetylase is derived from aprotozoal or fungal source.

The terms “histone deacetylase inhibitor” and “inhibitor of histonedeacetylase” are intended to mean a compound having a structure asdefined herein, which is capable of interacting with a histonedeacetylase and inhibiting its enzymatic activity.

The term “inhibiting histone deacetylase enzymatic activity” is intendedto mean reducing the ability of a histone deacetylase to remove anacetyl group from a protein, such as but not limited to a histone ortubulin. The concentration of inhibitor which reduces the activity of ahistone deacetylase to 50% of that of the uninhibited enzyme isdetermined as the IC₅₀ value. In some embodiments, such reduction ofhistone deacetylase activity is at least 50%, alternatively at leastabout 75%, and alternatively at least about 90%. In other embodiments,histone deacetylase activity is reduced by at least 95%, alternativelyby at least 99%.

In certain embodiments, such inhibition is specific, i.e., the histonedeacetylase inhibitor reduces the ability of a histone deacetylase toremove an acetyl group from a protein at a concentration that is lowerthan the concentration of the inhibitor that is required to produceanother, unrelated biological effect. For example, the concentration ofthe inhibitor required for histone deacetylase inhibitory activity is atleast 2-fold lower, alternatively at least 5-fold lower, alternativelyat least 10-fold lower, and alternatively at least 20-fold lower thanthe concentration required to produce an unrelated biological effect.

The term “protecting group” is intended to mean a group used insynthesis to temporarily mask the characteristic chemistry of afunctional group because it interferes with another reaction. A goodprotecting group should be easy to put on, easy to remove and in highyielding reactions, and inert to the conditions of the reactionrequired. A protecting group or protective group is introduced into amolecule by chemical modification of a functional group in order toobtain chemoselectivity in a subsequent chemical reaction. One skilledin the art will recognize that during any of the processes forpreparation of the compounds in the present invention, it may benecessary and/or desirable to protect sensitive or reactive groups onany of the molecules concerned. This may be achieved by means ofconventional protecting groups, such as but not limited to Bn- (or—CH₂Ph), —CHPh₂, allot (or CH₂═CH—CH₂—O—C(O)—), BOC-, -Cbz (or Z-),—F-moc, —C(O)—CF₃, N-Phthalimide,1-Adoc-, TBDMS-, TBDPS-, TMS-, TIPS-,IPDMS-, —SiR₃, SEM-, t-Bu-, Tr-, THP- and Allyl- and those described instandard textbooks, such as Greene, T. W. et al., Protective Groups inOrganic Synthesis, Wiley, N.Y. (1999). These protecting groups may beremoved at a convenient stage using methods known from the art. When afunctional group is termed “protected”, this means that the group is inmodified form to mitigate, especially preclude, undesired side reactionsat the protected site.

The compounds of the present invention form salts which are also withinthe scope of this invention. Reference to a compound of the invention,for example a compound of Formula (I), herein is understood to includereference to salts thereof, unless otherwise indicated.

The term “salt(s)”, as employed herein, denotes acidic and/or basicsalts formed with inorganic and/or organic acids and bases. In addition,when a compound of Formula (I) contains both a basic moiety, such as butnot limited to a pyridine or imidazole, and an acidic moiety such as butnot limited to a carboxylic acid, zwitterions (“inner salts”) may beformed and are included within the term “salt(s)” as used herein.Pharmaceutically acceptable (i.e., non-toxic (exhibiting minimal or noundesired toxicological effects), physiologically acceptable) salts arepreferred, although other salts are also useful, e.g., in isolation orpurification steps which may be employed during preparation. Salts ofthe compounds of the invention may be formed, for example, by reacting acompound of the present invention with an amount of acid or base, suchas an equivalent amount, in a medium such as one in which the saltsprecipitates or in an aqueous medium followed by lyophilization.

The compounds of the present invention which contain a basic moiety,such as but not limited to an amine or a pyridine or imidazole ring, mayform salts with a variety of organic and inorganic acids. Exemplary acidaddition salts include acetates (such as those formed with acetic acidor trihaloacetic acid, for example, trifluoroacetic acid), adipates,alginates, ascorbates, aspartates, benzoates, benzenesulfonates,bisulfates, borates, butyrates, citrates, camphorates,camphorsulfonates, cyclopentanepropionates, digluconates,dodecylsulfates, ethanesulfonates, fumarates, glucoheptanoates,glycerophosphates, hemisulfates, heptanoates, hexanoates,hydrochlorides, hydrobromides, hydroiodides, hydroxyethanesulfanotes(e.g., 2-hydroxyethanesulfonates), lactates, maleates,methanesulfonates, naphthalenesulfonates (e.g.,2-naphthalenesulfonates), nicotinates, nitrates, oxalates, pectinates,persulfates, phenylpropionates (e.g., 3-phenylpropionates), phosphates,picrates, pivalates, propionates, salicylates, succinates, sulfates(such as those formed with sulfuric acid), sulfonates, tartrates,thiocyanates, toluenesulfonates such as tosylates, undecanoates, and thelike.

The compounds of the present invention which contain an acidic moiety,such as but not limited to a carboxylic acid, may form salts with avariety of organic and inorganic bases. Exemplary basic salts includeammonium salts, alkali metal salts such as sodium, lithium and potassiumsalts, alkaline earth metal salts such as calcium and magnesium salts,salts with organic bases (for example, organic amines) such asbenzathines, dicyclohexylamines, hydrabamines (formed withN,N-bis(dehydroabietyl)ethylenediamine), N-methyl-D-glucamines,N-methyl-D-glycamides, t-butyl amines, and salts with amino acids suchas arginine, lysine and the like. Basic nitrogen-containing groups maybe quaternized with agents such as lower alkyl halides (e.g. methyl,ethyl, propyl and butyl chlorides, bromides and iodides), dialkylsulfates (e.g. dimethyl, diethyl, dibuty and diamyl sulfates), longchain halides (e.g. decyl, lauryl, myristyl and stearyl chlorides,bromides and iodides), aralkyl halides (e.g. benzyl and phenethylbromides), and others.

As used herein, the term “pharmaceutically acceptable salts” is intendedto mean salts that retain the desired biological activity of theabove-identified compounds and exhibit minimal or no undesiredtoxicological effects.

Another aspect of the invention provides compositions including acompound, N-oxide, hydrate, solvate, pharmaceutically acceptable salt,complex or prodrug of a compound according to the present invention asdescribed herein, or a racemic mixture, diastereomer, enantiomer ortautomer thereof. For example, in one embodiment of the invention, acomposition comprises a compound, N-oxide, hydrate, solvate,pharmaceutically acceptable salt, complex or prodrug of a compoundaccording to the present invention as described herein present in atleast about 30% enantiomeric or diastereomeric excess. In certaindesirable embodiments of the invention, the compound, N-oxide, hydrates,solvate, pharmaceutically acceptable salt, complex or prodrug is presentin at least about 50%, at least about 80%, or even at least about 90%enantiomeric or diastereomeric excess. In certain other desirableembodiments of the invention, the compound, N-oxide, hydrate, solvate,pharmaceutically acceptable salt, complex or prodrug is present in atleast about 95%, alternatively at least about 98% and alternatively atleast about 99% enantiomeric or diastereomeric excess. In otherembodiments of the invention, a compound, N-oxide, hydrate, solvate,pharmaceutically acceptable salt, complex or prodrug is present as asubstantially racemic mixture.

Some compounds of the invention may have chiral centers and/or geometricisomeric centers (E- and Z-isomers), and it is to be understood that theinvention encompasses all such optical, enantiomeric, diastereoisomericand geometric isomers. The invention also comprises all tautomeric formsof the compounds disclosed herein. Where compounds of the inventioninclude chiral centers, the invention encompasses the enantiomericallyand/or diasteromerically pure isomers of such compounds, theenantiomerically and/or diastereomerically enriched mixtures of suchcompounds, and the racemic and scalemic mixtures of such compounds. Forexample, a composition may include a mixture of enantiomers ordiastereomers of a compound of Formula (I) in at least about 30%diastereomeric or enantiomeric excess. In certain embodiments of theinvention, the compound is present in at least about 50% enantiomeric ordiastereomeric excess, in at least about 80% enantiomeric ordiastereomeric excess, or even in at least about 90% enantiomeric ordiastereomeric excess. In certain embodiments of the invention, thecompound is present in at least about 95%, alternatively in at leastabout 98% enantiomeric or diastereomeric excess, and alternatively in atleast about 99% enantiomeric or diastereomeric excess.

The chiral centers of the present invention may have the S or Rconfiguration. The racemic forms can be resolved by physical methods,such as, for example, fractional crystallization, separation orcrystallization of diastereomeric derivates or separation by chiralcolumn chromatography. The individual optical isomers can be obtainedeither starting from chiral precursors/intermediates or from theracemates by any suitable method, including without limitation,conventional methods, such as, for example, salt formation with anoptically active acid followed by crystallization.

The present invention also includes prodrugs of compounds of theinvention. The term “prodrug” is intended to mean a derivative of acompound of the present invention that requires a transformation, forexample, within the body, to release or activate the parent compound.Prodrugs are frequently, although not necessarily, pharmacologicallyinactive until converted to the parent compound. A hydroxyl containingcompound may be converted to, for example, a sulfonate, ester orcarbonate prodrug, which may be hydrolyzed in vivo to provide thehydroxyl compound. An amino containing compound may be converted, forexample, to a carbamate, amide, enamine, imine, N-phosphonyl,N-phosphoryl or N-sulfenyl prodrug, which may be hydrolyzed in vivo toprovide the amino compound. A carboxylic acid compound may be convertedto an ester (including silyl esters and thioesters), amide or hydrazideprodrug, which be hydrolyzed in vivo to provide the carboxylic acidcompound. Prodrugs for drugs which have functional groups different thanthose listed above are well known to the skilled artisan. Additionally,prodrugs can be converted to the compounds of the present invention bychemical or biochemical methods in an ex vivo environment. For example,prodrugs can be slowly converted to the compounds of the presentinvention when placed in a transdermal patch reservoir with a suitableenzyme or chemical reagent.

Prodrugs of compounds of the invention include compounds wherein ahydroxy, amino, carboxylic, or a similar group is modified. Examples ofprodrugs include, but are not limited to esters (e.g., acetate, formate,and benzoate derivatives), carbamates (e.g., N,N-dimethylaminocarbonyl)of hydroxy or amino functional groups in compounds of Formula (I)),amides (e.g., trifluoroacetylamino, acetylamino, and the like), and thelike.

The compounds of the invention may be administered as is or as aprodrug, for example in the form of an in vivo hydrolyzable ester or invivo hydrolyzable amide. An in vivo hydrolyzable ester of a compound ofthe invention containing carboxy or hydroxy group is, for example, apharmaceutically acceptable ester which is hydrolyzed in the human oranimal body to produce the parent acid or alcohol. Suitablepharmaceutically acceptable esters for carboxy include C₁-C₆alkoxymethyIesters (e.g., methoxymethyl), C₁-C₆alkanoyloxymethyl esters (e.g., forexample pivaloyloxymethyl), phthalidyl esters, C₃-C₈cycloalkoxycarbonyloxy-C₁-C₆alkyl esters (e.g.,1-cyclohexylcarbonyloxyethyl); 1,3-dioxolen-2-onylmethyl esters (e.g.,5-methyl-1,3-dioxolen-2-onylmethyl; and C₁-C₆alkoxycarbonyloxyethylesters (e.g., 1-methoxycarbonyloxyethyl) and may be formed at anyappropriate carboxy group in the compounds of this invention.

An in vivo hydrolyzable ester of a compound of the invention containinga hydroxy group includes inorganic esters such as phosphate esters andα-acyloxyalkyl ethers and related compounds which as a result of the invivo hydrolysis of the ester breakdown to give the parent hydroxy group.Examples of α-acyloxyalkyl ethers include acetoxymethoxy and2,2-dimethylpropionyloxy-methoxy. A selection of in vivo hydrolyzableester forming groups for hydroxy include alkanoyl, benzoyl, phenylacetyland substituted benzoyl and phenylacetyl, alkoxycarbonyl (to give alkylcarbonate esters), dialkylcarbamoyl andN—(N,N-dialkylaminoethyl)-N-alkylcarbamoyl (to give carbamates),N,N-dialkylaminoacetyl and carboxyacetyl. Examples of substituents onbenzoyl include morpholino and piperazino linked from a ring nitrogenatom via a methylene group to the 3- or 4-position of the benzoyl ring.A suitable value for an in vivo hydrolyzable amide of a compound of theinvention containing a carboxy group is, for example, a N—C₁-C₆alkyl orN,N-di-C₁-C₆alkyl amide such as N-methyl, N-ethyl, N-propyl,N,N-dimethyl, N-ethyl-N-methyl or N,N-diethyl amide.

Upon administration to a subject, the prodrug undergoes chemicalconversion by metabolic or chemical processes to yield a compound of thepresent invention, or a salt and/or solvate thereof. Solvates of thecompounds of the present invention include, for example, hydrates.

Typically, in a prodrug, a polar functional group (e.g., a carboxylicacid, an amino group, a hydroxyl group, etc.) is masked by a promoiety,which is labile under physiological conditions. ““Promoiety”” refers toa form of protecting group that when used to mask a functional groupwithin a compound molecule converts the drug into a prodrug. Typically,the promoiety will be attached to the compound via bond(s) that arecleaved by enzymatic or non-enzymatic means in vivo.

The terms “protect”, “protected”, and “protecting” are intended to referto a process in which a functional group in a chemical compound isselectively masked by a non-reactive functional group in order to allowa selective reaction(s) to occur elsewhere on said chemical compound.Such non-reactive functional groups are herein termed “protectinggroups”. For example, the term “nitrogen protecting group”, is intendedto mean a group capable of selectively masking the reactivity of anitrogen (N) group. The term “suitable protecting group” is intended tomean a protecting group useful in the preparation of the compounds ofthe present invention. Such groups are generally able to be selectivelyintroduced and removed using mild reaction conditions that do notinterfere with other portions of the subject compounds. Protectinggroups that are suitable for use in the processes and methods of thepresent invention are well known, such as but not limited to, Bn- (or—CH₂Ph), —CHPh₂, alloc (or CH₂═CH—CH₂—O—C(O)—), BOC-, -Cbz (or Z-),—F-moc, —C(O)—CF₃, N-Phthalimide, 1-Adoc-, TBDMS-, TBDPS-, TMS-, TIPS-,IPDMS-, —SiR₃, SEM-, t-Bu-, Tr-, THP- and Allyl-. These protectinggroups may be removed at a convenient stage using methods known from theart. The chemical properties of such protecting groups, methods fortheir introduction and their removal art known in the art and can befound for example in T. Greene and P. Wuls, Protective Groups in OrganicSynthesis (3rd ed.), John Wiley & Sons, NY (1999), herein incorporatedby reference in its entirety. The terms “deprotect”, “deprotected”, and“deprotecting” are intended to refer to the process of removing aprotecting group from a compound.

Throughout the specification, certain embodiments of one or morechemical substituents are identified. Also encompassed are combinationsof such embodiments. For example, the invention describes certainembodiments of L in the compounds and describes certain embodiments ofgroup Y. Thus, as an example, also contemplated as within the scope ofthe invention are compounds in which certain examples of L are asdescribed and in which certain examples of group Y are as described.

The foregoing merely summarizes one aspect and embodiments of theinvention and is not intended to be limiting in nature. This aspect andembodiments are described more fully below.

Compounds

In one aspect, the invention provides compounds of the formula (I):

and N-oxides, hydrates, solvates, pharmaceutically acceptable salts,prodrugs and complexes thereof, and racemic and scalemic mixtures,tautomers, diastereomers and enantiomers thereof, wherein

is selected from the group consisting of aryl, heteroaryl, cycloalkyland heterocyclyl, wherein each aryl, heteroaryl, cycloalkyl andheterocyclyl moiety is optionally substituted;

-   W is selected from the group consisting of N, —C═ and —C(R¹)—,    wherein when

is cycloalkyl or heterocyclyl, then W is —C(R¹)—;

-   M is selected from the group consisting of —C(O)N(R¹)OR²,    —C(O)NR¹R², —C(O)OH, —C(O)OR¹, —C(O)C₁-C₃alkyl-SR¹,    —NHC(O)C₁-C₃alkyl-SR¹, —NHC(O)C₁-C₃alkyl-OR¹, —C(O)CH₂—S(acetyl),    —C(O)-heteroaryl, —C(O)-heterocyclyl, —C(NOH)NR¹R²,    —C(O)C₁-C₃alkyl-OR¹, —C(O)C₁-C₃alkyl-NR¹R², —C(O)CF₃, —C(O)C(O)OR¹,    —C(O)C(O)NR¹R², —C(O)C₁-C₄alkyl, —N(OH)C(O)H, —N(OR¹)C(O)R²,    —NR¹SO₂NR¹R², —SO₂NR¹OH, —N(OH)C(O)NR¹R², —NR¹C(O)N(OH)R²,    —OC(O)N(OH)R², —C(NOH)NR¹R², and a Zn-chelating group;    or-   M is —C₁-C₂alkyl-C(O)N(R¹)OR², when

-   R¹ and R² is independently selected from the group consisting of —H,    -alkyl, -aryl, -aryl-aryl, -hetetoaryl, heteroaryl-aryl,    heteroaryl-heteroaryl, alkyl-heteroaryl and -alkyl-aryl, wherein    each aryl and heteroaryl moiety is optionally substituted;-   R is selected from the group consisting of H, alkyl, halo, hydroxy,    nitro, C₁-C₄alkyl, —NR¹R², —OR¹, aryl, heteroaryl, alkyloxy and CF₃;-   n is an integer from 0 to 1;-   L is selected from the group consisting of aryl, heteroaryl,    cycloalkyl, heterocyclyl, fused aryl, fused heterocyclyl, fused    cycloalkyl, -alkenyl-aryl, -aryl-heteroaryl, -heteroaryl-aryl,    -alkynyl-aryl, —O—C₀-C₄alkyl-aryl, -alkyl-aryl,    —SO₂NR¹—C₀-C₄alkyl-aryl, —NR¹-aryl, —CF₃, -t-Bu, —NR¹SO₂-aryl, halo,    —N(R¹)C(O)-aryl, —S-heteroaryl and —S-aryl, wherein each aryl,    heteroaryl, cycloalkyl and heterocyclyl moiety is optionally    substituted with 1 to 3 independently selected substituents, and    each of which is optionally fused to one or more aryl, heterocyclic    or heteroaryl rings, or one or more saturated or partially    unsaturated cycloalkyl or heterocyclyl rings, each of which ring is    optionally substituted, wherein a cycloalkyl, heterocyclyl, aryl or    heteroaryl moiety in

is optionally connected to a cycloalkyl, heterocyclyl, aryl orheteroaryl in L by a bond or by a bridging substituent;

-   Y is selected from the group consisting of H, halo,    -aryl-heterocyclyl, -aryl-O—C₀-C₄alkyl-aryl, -aryl-aryl,    —C₁-C₄alkyl, heteroalkyl, alkenyl, alkynyl, —N(R^(a))(R^(b)),    —N(R^(c))(R^(d)), —OR^(e), —SR^(s), —C₀-C₃alkyl-aryl,    —C₀-C₃alkyl-heteroaryl, —C₀-C₃alkyl-heterocyclyl,    —C₀-C₃alkyl-cycloalkyl, —C₂-C₄alkenyl-aryl,    —C₂-C₄alkenyl-heteroaryl, —C₂-C₄alkenyl-heterocyclyl,    —C₂-C₄alkenyl-cycloalkyl, —C₂-C₄alkynyl-aryl,    —C₂-C₄alkynyl-heteroaryl, —C₂-C₄alkynyl-heterocyclyl, —C₂-C₄alkynyl    -cycloalkyl, —O—C₀-C₃alkyl-aryl, —O—C₀-C₃alkyl-heteroaryl,    —O—C₀-C₃alkyl-cycloalkyl, —O—C₀-C₃alkyl-heterocycloalkyl,    —C(O)NH—C₀-C₃alkyl-aryl, —C(O)NH—C₀-C₃alkyl-heteroaryl,    —O—C₀-C₃alkyl-aryl-aryl, —O—C₀-C₃alkyl-heteroaryl-aryl,    —O—C₀-C₃alkyl-aryl-heteroaryl, —O—C₀-C₃alkyl-heteroaryl-heteroaryl,    —S(O)₀₋₂—C₀-C₃alkyl-aryl, —S(O)₀₋₂—C₀-C₃alkyl-heteroaryl-aryl,    —S(O)₀₋₂—C₀-C₃alkyl-aryl-aryl, —S(O)₀₋₂—C₀-C₃alkyl-heteroaryl,    —S(O)₀₋₂—C₀-C₃alkyl-aryl-heteroaryl,    —S(O)₀₋₂—C₀-C₃alkyl-heteroaryl-heteroaryl, -aryl-C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-aryl,    —C₀-C₃alkyl-aryl-C₀-C₂alkyl-N(R^(e))—C₀-C₂alkyl-aryl,    —C₀-C₃alkyl-aryl-C₀-C₂alkyl-N(R^(e))—C₀-C₂alkyl-heteroaryl,    —C₀-C₃alkyl-heteroaryl-C₀-C₂alkyl-N(R^(e))—C₀-C₂alkyl-aryl,    —C₀-C₃alkyl-heteroaryl-C₀-C₂alkyl-N(R^(e))—C₀-C₂alkyl-heteroaryl,    —C₀-C₂alkyl-aryl-C₀-C₂alkyl-N(R^(e))—S(O)₂—C₀-C₂alkyl-aryl,    —C₀-C₃alkyl-aryl-C₀-C₂alkyl-N(R^(e))—S(O)₂—C₀-C₂alkyl-heteroaryl,    C₀-C₃alkyl-heteroaryl-C₀-C₂alkyl-N(R^(e))—S(O)₂—C₀-C₂alkyl-aryl,    —C₀-C₃alkyl-heteroaryl-C₀-C₂alkyl-N(R^(e))—S(O)₂—C₀-C₂alkyl-heteroaryl,    N(R^(e))—S(O)₂—N(R^(f))H, —N(R^(e))—S(O)₂—N(R^(f))₂,    —N(R^(e))—C(O)H, —N(R^(e))—C(O)alkyl, —C(O)—N(R^(e))H,    —C(O)—N(R^(e))₂, —N(R^(e))—C(O)—N(R^(f))₂, —N(R^(e))—C(O)—O-alkyl,    —O—C(O)—N(R^(e))(R^(f)), —OH, —O-alkyl, —O-aryl,    —N(R^(e))—C(O)—C₂-C₄alkyl-OR^(e), —O—C₂-C₄alkyl-N(R^(e))(R^(f)),    -heterocyclyl-C₀-C₃alkyl-aryl, -cycloalkyl-C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-heteroaryl, -heteroaryl-C₀-C₃alkyl-heteroaryl,    -heterocyclyl-C₀-C₃alkyl-heteroaryl,    -cycloalkyl-C₀-C₃alkyl-heteroaryl, -aryl-C₀-C₃alkyl-heterocyclyl,    -heteroaryl-C₀-C₃alkyl-heterocyclyl,    -heterocyclyl-C₀-C₃alkyl-heterocyclyl,    -cycloalkyl-C₀-C₃alkyl-heterocyclyl,    -heterocyclyl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -heterocyclyl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -heterocyclyl-C₀-C₃alkyl-O—C(O)NH—C₀-C₃alkyl-aryl,    -heterocyclyl-C₀-C₃alkyl-O—C(O)NH—C₀-C₃alkyl-heteroaryl,    -heterocyclyl-C₀-C₃alkyl-heteroaryl-aryl,    -heterocyclyl-C₀-C₃alkyl-heteroaryl-heteroaryl,    -heterocyclyl-C₀-C₃alkyl-aryl-aryl, —NHS(O)₂—C₀-C₃alkyl-aryl,    —NHS(O)₂—C₀-C₃alkyl-heteroaryl, —NHC(O)—C₀-C₃alkyl-aryl,    -heterocyclyl-C₀-C₃alkyl-aryl, -heterocyclyl-C₀-C₃alkyl-heteroaryl,    -heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl,    -heterocyclyl-S(O)₂-alkyl, -heterocyclyl-S(O)₂—C₀-C₃alkyl-aryl,    -heterocyclyl-S(O)₂—C₀-C₃alkyl-heteroaryl,    -heterocyclyl-C₁-C₄alkyl-aryl, -heterocyclyl-C₁-C₄alkyl-heteroaryl,    -   -heterocyclyl-C₀-C₃alkyl-aryl-heteroaryl,        -   -heterocyclyl-C₀-C₃alkyl-heteroaryl-C₀-C₃alkyl-aryl,        -   -heterocyclyl-C₀-C₃alkyl-heteroaryl-C₀-C₃alkyl-heteroaryl,        -   -heterocyclyl-C₀-C₃alkyl-aryl-C₀-C₃alkyl-aryl,        -   -heterocyclyl-C₀-C₃alkyl-aryl-C₀-C₃alkyl-heteroaryl,        -   -heterocyclyl-S(O)₂—C₀-C₃alkyl-aryl,            -heterocyclyl-S(O)₂—C₀-C₃alkyl-heteroaryl,        -   -heterocyclyl-S(O)₂—C₀-C₃alkyl-alkyl,            -heterocyclyl-S(O)₂—C₀-C₃alkyl-cycloalkyl,        -   -heterocyclyl-S(O)₂—C₀-C₃alkyl-heterocyclyl,            -heterocyclyl-C(O)—C₀-C₃alkyl-aryl,        -   -heterocyclyl-C(O)—C₀-C₃alkyl-heteroaryl,            -heterocyclyl-C(O)—C₀-C₃alkyl-alkyl,        -   -heterocyclyl-C(O)—C₀-C₃alkyl-cycloalkyl,        -   -heterocyclyl-C(O)—C₀-C₃alkyl-heterocyclyl,        -   -heterocyclyl-C(O)NH—C₀-C₃alkyl-aryl,        -   -heterocyclyl-C(O)NH—C₀-C₃alkyl-heteroaryl,        -   -heterocyclyl-C(O)NH—C₀-C₃alkyl-alkyl,        -   -heterocyclyl-C(O)NH—C₀-C₃alkyl-cycloalkyl,        -   -heterocyclyl-C(O)NH—C₀-C₃alkyl-heterocyclyl,        -   -heterocyclyl-C(O)O—C₀-C₃alkyl-aryl,        -   -heterocyclyl-C(O)O—C₀-C₃alkyl-heteroaryl,        -   -heterocyclyl-C(O)O—C₀-C₃alkyl-alkyl,        -   -heterocyclyl-C(O)O—C₀-C₃alkyl-cycloalkyl,        -   -heterocyclyl-C(O)O—C₀-C₃alkyl-heterocyclyl,        -   -heterocyclyl-S(O)₂—NH—C₀-C₃alkyl-aryl,        -   -heterocyclyl-S(O)₂—NH—C₀-C₃alkyl-heteroaryl,        -   -heterocyclyl-S(O)₂—NH—C₀-C₃alkyl-alkyl,        -   -heterocyclyl-S(O)₂—NH—C₀-C₃alkyl-cycloalkyl,        -   -heterocyclyl-S(O)₂—NH—C₀-C₃alkyl-heterocyclyl,        -   —C₀-C₃alkyl-heterocyclyl-C₂-C₄alkenyl-aryl,            —C₀-C₃alkyl-heterocyclyl-CH(aryl)₂,        -   —C₀-C₃alkyl-heterocyclyl-CH(heteroaryl)₂,        -   —C₀-C₃alkyl-heterocyclyl-CH(aryl)(heteroaryl),        -   —C₀-C₃alkyl-aryl-O—C₂-C₄alkyl-heterocyclyl,        -   —C₀-C₃alkyl-aryl-C₀-C₃alkyl-heterocyclyl-C₀-C₃alkyl-aryl,        -   —C₀-C₃alkyl-heteroaryl-C₀-C₃alkyl-heterocyclyl-C₀-C₃alkyl-aryl,        -   —C₀-C₃alkyl-aryl-C₀-C₃alkyl-heterocyclyl-C₀-C₃alkyl-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-C₀-C₃alkyl-heterocyclyl-C₀-C₃alkyl-heteroaryl,            —NH—C(O)-aryl, —NH—C(O)-heteroaryl, —CH(aryl)₂,            —CH(heteroaryl)₂,        -   —C₀-C₃alkyl-aryl-heterocyclyl,            —C₀-C₃alkyl-aryl-heterocyclyl-S(O)₂-aryl,        -   —C₀-C₃alkyl-heteroaryl-heterocyclyl-S(O)₂-aryl,        -   —C₀-C₃alkyl-aryl-heterocyclyl-S(O)₂-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-heterocyclyl-S(O)₂-heteroaryl,        -   —C₀-C₃alkyl-aryl-S(O)₂-heterocyclyl-aryl,        -   —C₀-C₃alkyl-heteroaryl-S(O)₂-heterocyclyl-aryl,        -   —C₀-C₃alkyl-aryl-S(O)₂-heterocyclyl-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-S(O)₂-heterocyclyl-heteroaryl,        -   —C₀-C₃alkyl-aryl-heterocyclyl-C(O)-aryl,        -   —C₀-C₃alkyl-heteroaryl-heterocyclyl-C(O)-aryl,        -   —C₀-C₃alkyl-aryl-heterocyclyl-C(O)-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-heterocyclyl-C(O)-heteroaryl,        -   —C₀-C₃alkyl-aryl-C(O)-heterocyclyl-aryl,        -   —C₀-C₃alkyl-heteroaryl-C(O)-heterocyclyl-aryl,        -   —C₀-C₃alkyl-aryl-C(O)-heterocyclyl-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-C(O)-heterocyclyl-heteroaryl,        -   —C₀-C₃alkyl-aryl-heterocyclyl-C(O)N(R^(e))-aryl,        -   —C₀-C₃alkyl-heteroaryl-heterocycyl-C(O)N(R^(e))-aryl,        -   —C₀-C₃alkyl-aryl-heterocycyl-C(O)N(R^(e))-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-heterocycyl-C(O)N(R^(e))-heteroaryl,        -   —C₀-C₃alkyl-aryl-N(R^(e))C(O)-heteroaryl-aryl,        -   —C₀-C₃alkyl-heteroaryl-N(R^(e))C(O)-heterocycyl-aryl,        -   —C₀-C₃alkyl-aryl-N(R^(e))C(O)-heterocyclyl-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-N(R^(e))C(O)-heterocyclyl-heteroaryl,        -   —C₀-C₃alkyl-aryl-heterocyclyl-C(O)O-aryl,        -   —C₀-C₃alkyl-heteroaryl-heterocyclyl-C(O)O-aryl,        -   —C₀-C₃alkyl-aryl-heterocyclyl-C(O)O-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-heterocyclyl-C(O)O-heteroaryl,        -   —C₀-C₃alkyl-aryl-OC(O)-heterocyclyl-aryl,        -   —C₀-C₃alkyl-heteroaryl-OC(O)-heterocyclyl-aryl,        -   —C₀-C₃alkyl-aryl-OC(O)-heterocyclyl-heteroaryl,        -   —C₀-C₃alkyl-heteroaryl-OC(O)-heterocyclyl-heteroaryl,            aromatic polycycles, non-aromatic polycycles, polyheteroaryl            groups, non-aromatic polyheterocyclic, mixed aryl and            non-aryl polyheterocycle, —Z¹—Z—Z²-D, —C₀-C₂alkyl-Z—Z³—Z-D,            —CH(OR¹)—Z—Z³—Z-D, —C(R¹)(R²)—Z—Z³—Z-D, —C(F)₂—Z—Z³—Z-D,            fused heterocyclyl, —C(O)—N(R¹)—C₀-C₃alkyl-aryl-O-aryl,            —C(O)—N(R¹)—C₀-C₃alkyl-aryl-S(O)₀₋₂-aryl,            —C(O)—N(R¹)—C₀-C₃alkyl-aryl-N(R²)-aryl,            —C(O)—N(R¹)—C₀-C₃alkyl-aryl-O-heteraryl,            —C(O)—N(R¹)—C₀-C₃alkyl-aryl-S(O)₀₋₂-heteroaryl,            —C(O)—N(R¹)—C₀-C₃alkyl-aryl-N(R²)-heteroaryl,            —C(O)—N(R¹)—C₀-C₃alkyl-heteroaryl-O-aryl,            —C(O)—N(R¹)—C₀-C₃alkyl-heteroaryl-S(O)₀₋₂-aryl,            —C(O)—N(R¹)—C₀-C₃alkyl-heteroaryl-N(R²)-aryl,            —C(O)—N(R¹)—C₀-C₃alkyl-heteroaryl-O-heteroaryl,            —C(O)—N(R¹)—C₀-C₃alkyl-heteroaryl-S(O)₀₋₂-heteroaryl,            —C(O)—N(R¹)—C₀-C₃alkyl-heteroaryl-N(R²)-heteroaryl,            wherein each aryl, heteroaryl, cycloalkyl and heterocyclyl            moiety is optionally substituted,            wherein-   Z¹ is selected from the group consisting of chemical bond, alkyl,    aryl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl,    cycloalkyl, heteroaryl, —C(F)(R¹)—, —C(OR₂)(R¹)—, —C(aryl)(R¹)—,    —C(heteroaryl)(R¹)—, —C(heterocyclyl)(R¹)—, —C(cycloalkyl)(R¹)—,    —C(alkyl)(R¹)—, —C(alkenyl)(R¹)—, —C(alkynyl)(R¹)—, wherein each    aryl, heteroaryl, cycloalkyl and heterocyclyl moiety is optionally    substituted and each of which is optionally fused to one or more    aryl or heteroaryl rings, or one or more saturated or partially    unsaturated cycloalkyl or heterocyclyl rings, each of which ring is    optionally substituted;-   Z is selected from the group consisting of chemical bond, —O—,    —N(R¹)—, —N(R^(a))(R^(b)), —N(R^(c)C)—, —N(C₂-C₄alkyl-OR¹)—, —C(O)—,    —C(NOR¹)—, —C(H)(F)—, —C(H)(CON(R¹)(R²))—CON(R¹)(R²)—,    —C(H)(N(R¹)(R²)), —C(O)N(R¹)(R²)—,    —C(H)(CON(R^(e))(R^(f)))—C(O)N(R¹)(R²)—,    —C(H)(N(R^(e))(R^(f)))—C(O)N(R¹)(R²)—,    —C(H)(heteroaryl)-C(O)N(R¹)(R²)—,    —C(H)(heteroaryl-aryl)-C(O)N(R¹)(R²)—,    —C(H)(heteroaryl-heteroaryl)-C(O)N(R¹)(R²)—, —C(O)—C(O)N(R¹)—,    —S(O)₀₋₂—, —N(R¹)S(O)₂—, —S(O)₂N(R¹)—, —N(R¹)S(O)₂N(R²)—,    —N(R¹)C(O)—, —C(O)N(R¹)—, —OC(O)—, —C(O)O—, —N(R¹)C(NR²)—,    —C(NR²)N(R¹)—, —N(R¹)C(O)N(R²)—, —N(R¹)C(O)O—, —OC(O)N(R¹)—,    —N(R¹)C(S)—, —C(S)N(R¹)—, —N(R¹)C(S)N(R²)—, —N(R¹)C(S)O—,    —OC(S)N(R¹)—, —O—C₂-C₄alkyl-N(R¹)—, —N(R¹)—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-N(R^(c))—, N(R^(c))—C₂-C₄alkyl-O—,    —O-alkyl-C₁-C₄alkyl-S(O)₂N(R¹)—, —S(O)₂N(R¹)—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-N(R¹)S(O)₂—, —N(R¹)S(O)₂—C₁-C₄alkyl-O—,    —C(O)—C₁-C₄alkyl-N(R¹)—, —N(R¹)—C₁-C₄alkyl-C(O)—,    —O—C₁-C₄alkyl-C(O)N(R¹)—, —C(O)N(R¹)—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-N(R¹)C(O)—, —N(R¹)C(O)—C₁-C₄alkyl-O—,    —O—C₁-C₄alkyl-C(O)—, —C(O)—C₁-C₄alkyl-O—, —N(R¹)—C₁-C₄alkyl-C(O)—,    —C(O)—C₁-C₄alkyl-N(R¹)—, —O—C₁-C₄alkyl-C(S)—, —C(S)—C₁-C₄alkyl-O—,    —N(R¹)—C₁-C₄alkyl-C(S), —C(S)—C₁-C₄alkyl-N(R¹)—,    —N(R¹)—C₁-C₄alkyl-C(S)—, —O—C₁-C₄alkyl-C(S)N(R¹)—,    —C(S)N(R¹)—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-N(R¹)—C(S)—,    —N(R¹)C(S)—C₁-C₄alkyl-O—, —N(R¹)—C₁-C₄alkyl-S(O)₂—,    —O—C₁-C₄alkyl-S(O)₂N(R¹)—, —S(O)₂N(R¹)—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-N(R¹)S(O)₂—, —N(R¹)S(O)₂—C₁-C₄alkyl-O—,    —O—C₂-C₄alkyl-OC(O)N(R¹)—, —O—C₂-C₄alkyl-OC(S)N(R¹)—;-   Z² is selected from the group consisting of chemical bond, alkyl,    alkenyl, —C(F)(R¹)—, —C(OR²)(R¹)—, —C(aryl)(R¹)—,    —C(heteroaryl)(R¹)—, —C(heterocyclyl)(R¹)—, —C(cycloalkyl)(R¹)—,    —C(alkyl)(R¹)—, —C(alkenyl)(R¹)—, —C(alkynyl)(R¹)—, wherein each    alkyl, aryl, alkenyl or alkynyl moiety is optionally substituted;-   Z³ is selected from the group consisting of chemical bond,    C₂-C₅alkyl, aryl, heterocyclyl, bridged heterocyclyl, spiro    heterocyclyl, cycloalkyl or heteroaryl, wherein each aryl,    heteroaryl, cycloalkyl and heterocyclyl moiety is optionally    substituted and each of which is optionally fused to one or more    aryl or heteroaryl rings, or one or more saturated or partially    unsaturated cycloalkyl or heterocyclyl rings, each of each ring is    optionally substituted;-   D is selected from the group consisting of H, aryl, heteroaryl,    alkyl, cycloalkyl and heterocyclyl, bridged heterocyclyl, spiro    heterocyclyl, aryl-heterocyclyl, -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -aryl-C₀-C₃alkyl-N(R¹)—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-N(R¹)—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-N(R¹)—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-N(R¹)—C₀-C₃alkyl-heteroaryl, aromatic    polycycle, non-aromatic polycycle, polyheteroaryl group,    non-aromatic polyheterocyclic, mixed aryl and non-aryl    polyheterocycle, each of which is optionally substituted and each of    which is optionally fused to one or more aryl or heteroaryl rings,    or one or more saturated or partially unsaturated cycloalkyl or    heterocyclyl rings, each of which ring is optionally substituted;-   R^(a) and R^(b) together with the nitrogen to which they are bound    form a 4 to 7 membered heterocyclyl having 1 or 2 annular    heteroatoms, or a 5 to 8 membered bridged heterocyclyl having 1 or 2    annular heteroatoms, the heterocyclyl being optionally substituted    with 1-3 substituents independently selected from the group    consisting of H, OH, oxo (i.e., ═O), —N(R¹)(R²), C₁-C₆alkyl, aryl,    heteroaryl, —C₁-C₆alkyl-aryl, —C₁-C₆alkyl-heteroaryl,    —C₁-C₃alkoxy-C₁-C₃alkyl, —C₂-C₃alkyl-OH, —C₂-C₃alkyl-O—C₁-C₄alkyl,    —C₅-C₆cycloalkyl, —C₀-C₃alkyl-N(H)—C(O)—C₁-C₃alkyl,    —C₀-C₃alkyl-N(H)—C(O)-haloalkyl,    —C₀-C₃alkyl-NHC(O)O—C₁-C₃alkyl-aryl, —C₀-C₃alkyl-CF₃,    —C₀-C₃alkyl-NHC(O)O—C₁-C₃alkyl-heteroaryl and —C₀-C₃alkyl-NH₂,    wherein said heterocyclyl also is optionally fused to an aryl or    heteroaryl, wherein each aforementioned aryl, heteroaryl, cycloalkyl    and heterocyclyl moiety is optionally substituted;-   each R^(c) and R^(d) is independently selected from the group    consisting of H, —C₁-C₆alkyl, —C₂-C₃alkyl-OR^(e), —C(O)OR¹,    —C(O)NR¹R², —C(S)OR¹, —C(S)NR¹R², —C(O)R¹, —C(S)R¹, —S(O)₂R¹, —S(O)₂    NR¹R², aryl, heteroaryl, -heteroaryl-heteroaryl, -heteroaryl-aryl,    -aryl-heteroaryl, —C(O)-aryl, —C₁-C₃-alkoxy-C₁-C₃-alkyl,    —C₂-C₃alkyl-OR², —C₂-C₃alkyl-NR^(a)R^(b), —C₂-C₃alkyl-NR^(e)R^(f),    —CH₂—C(CH₃)₂—NR^(a)R^(b) and —CH₂—C(CH₃)₂—NR^(e)R^(f), in which each    aryl and heteroaryl is optionally substituted with one, two or three    substituents independently selected from amino, OCH₃ and OH;-   each R^(e) and R^(f) is independently selected from the group    consisting of —H, -alkyl, -aryl, -aryl-aryl, -hetetoaryl,    heterocyclyl, heteroaryl-aryl, heteroaryl-heteroaryl,    —C₁-C₆alkyl-C(O)NR¹R², —C(O)-alkyl, —C(O)heteroaryl,    —C(O)cycloalkyl, —C(O)aryl, —C(O)O-alkyl, —C(O)Oheteroaryl,    —C(O)Ocycloalkyl, —C(O)Oaryl, —C(O)N(R¹)-alkyl,    —C(O)N(R¹)heteroaryl, —C(O)(NR¹)cycloalkyl, —C(O)N(R¹)aryl and    —C(O)CF₃; and-   each R^(s) is independently selected from the group consisting of    —H, C₁-C₆alkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl and a    protecting group, wherein each cycloalkyl, heterocyclyl, aryl, alkyl    and heteroaryl moiety is optionally substituted,-   provided that Formula (I) excludes the following compounds    N-hydroxybiphenyl-2-carboxamide, 2-benzyl-N-hydroxybenzamide,    N-hydroxy-2-phenoxybenzamide, N-hydroxy-2-(phenylamino)benzamide,    N-hydroxy-4-phenyl-1H-pyrrole-3-carboxamide,    N-hydroxy-4-(naphthalen-1-yl)-1H-pyrrole-3-carboxamide,    N-hydroxy-4-(naphthalen-2-yl)-1H-pyrrole-3-carboxamide and provided    that Formula (I) excludes compounds having the formula

wherein R¹ is

R^(r) and R^(s) are independently H, lower haloalkyl, —CO₂H, —NO₂, loweralkyl carboxylate, lower alkoxy or —CN, and X is S or O.

In one embodiment of the present invention, the invention providescompounds of the Formula (Ia):

wherein groups L, W, X, Y, R and n are as described for Formula (I).

In one embodiment of Formula (Ia),

is selected from the group consisting of

wherein A¹, A², A³, A⁴ and A⁵ form a 5-membered heteroaryl ring, whereinA¹ and A³ are selected from the group consisting of carbon, nitrogen,—S— and —O—, A⁴ is carbon and A² and A⁵ are nitrogen or carbon, providedthat at least one of A² and A⁵ is carbon, and wherein * represents thepoint of attachment to group L and ** represents the point of attachmentto group Y.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ib):

wherein groups L, X, Y, R and n are as described for Formula (I).

In one embodiment of Formula (Ib),

is selected from the group consisting of

wherein A⁶, A⁷ and A⁸ form part of a 6-membered aryl or heteroaryl ring,wherein A⁶, A⁷ and A⁸ are independently carbon and/or nitrogen, providedthat at least one of A⁶, A⁷ and A⁸ in structures (c) and (d) is carbon,and wherein * represents the point of attachment to group L and **represents the point of attachment to group Y.

In an embodiment of the present invention,

is an aryl group, for example a 6-membered group.

In another embodiment of the present invention,

is a phenyl group.

In another embodiment of the present invention,

is a heteroaryl group, for example a 5- or 6-membered heteroaryl group.

In another embodiment of the present invention,

is imidazothiazolyl, benzofuranyl or benzothienyl for example,imidazo[2,1-b]thiazolyl.

In another embodiment of the present invention,

is benzothienyl.

In another embodiment of the present invention,

wherein * represents the point of attachment of L and

represents the point of attachment of M.

In another embodiment of the present invention,

is a 5-membered heteroaryl group.

In another embodiment of the present invention,

is a 5-membered heteroaryl group selected from the group consisting ofoxazolyl, thienyl, pyrazolyl, thiazolyl and isoxazolyl.

In another embodiment

is selected from the group consisting of pyrazolyl, thiazolyl andthienyl.

In another embodiment of the present invention,

is pyridyl or pryimidyl.

In another embodiment of the present invention,

is selected from group consisting of

wherein

represents the point of attachment to group M, * represents the point ofattachment to group L and ** represents the point of attachment to groupY.

In another embodiment of the present invention,

is selected from group consisting of

wherein

represents the point of attachment to group M, * represents the point ofattachment to group L and ** represents the point of attachment to groupY.

In another embodiment of the present invention,

is selected from group consisting of

wherein

represents the point of attachment to group M, * represents the point ofattachment to group L and ** represents the point of attachment to groupY.

In another embodiment of the present invention,

is selected from group consisting of

wherein

represents the point of attachment to group M, * represents the point ofattachment to group L and ** represents the point of attachment to groupY.

In another embodiment of the present invention,

is

wherein

represents the point of attachment to group M, * represents the point ofattachment to group L and ** represents the point of attachment to groupY.

In another embodiment of the present invention,

is selected from group consisting of

wherein

represents the point of attachment to group M, * represents the point ofattachment to group L and ** represents the point of attachment to groupY.

In another embodiment of the present invention, W is

wherein * is the point of attachment of group L.

In another embodiment of the present invention, M is —C(O)N(R¹)OR² or—N(OH)—C(O)H.

In another embodiment of the present invention, M is —C(O)N(R¹)OR², forexample, —C(O)NHOH.

In another embodiment of the present invention, R¹ is H or alkyl.

In another embodiment of the present invention, R² is H.

In another embodiment of the present invention, R is H.

In another embodiment of the present invention, n is 0.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, cycloalkyl, heterocyclyl, fusedaryl, fused heterocyclyl, fused cycloalkyl, -alkenyl-aryl,-aryl-heteroaryl, -heteroaryl-aryl, -alkynyl-aryl, —O—C₀-C₄alkyl-aryl,-alkyl-aryl, —SO₂—N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl, —CF₃, -t-Bu,—NR₁SO₂-aryl, halo, —N(R¹)C(O)-aryl and —S-aryl, wherein each aryl,heteroaryl, cycloalkyl and heterocyclyl moiety is optionallysubstituted.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, cycloalkyl, heterocyclyl, fusedaryl, fused heterocyclyl, fused cycloalkyl, -alkenyl-aryl,-aryl-heteroaryl, -heteroaryl-aryl, -alkynyl-aryl, —O—C₀-C₄alkyl-aryl,-alkyl-aryl, —SO₂NR₁—C₀-C₄alkyl-aryl, —NR₁-aryl, —CF₃, -t-Bu,—NR₁SO₂-aryl, halo, —N(R¹)C(O)-aryl and —S-aryl, wherein each aryl,heteroaryl, cycloalkyl and heterocyclyl moiety is optionally substitutedwith 1, 2 or 3 moieties independently selected from the group consistingof phenyl (which itself is optionally substituted with alkyl), halo,alkyl, alkoxy, NO₂, pyrrolyl, thienyl, amino, dialkylamino, morpholinyland —C(NOH)NH₂, and each of which is optionally fused to one or morearyl, heterocyclic or heteroaryl rings, or one or more saturated orpartially unsaturated cycloalkyl or heterocyclyl rings, each of eachring is optionally substituted.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, cycloalkyl, alkenyl-aryl,—O—C₀-C₄alkyl-aryl, -alkyl-aryl, —S(O)₂N(R¹)—C₀-C₄alkyl-aryl,—N(R¹)-aryl, —CF₃, —N(R¹)—S(O)₂-aryl, fused aryl, fused heterocyclyl andfused cycloalkyl, halo, —N(R¹)C(O)-aryl and —S-aryl, wherein each aryl,heteroaryl, cycloalkyl and heterocyclyl moiety is optionallysubstituted, and each of which is optionally fused to one or more aryl,heteroaryl or heterocyclyl rings, or one or more saturated or partiallyunsaturated cycloalkyl or heterocyclyl rings, each of which ring isoptionally substituted.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, cycloalkyl, alkenyl-aryl,—O—C₀-C₄alkyl-aryl, -alkyl-aryl, —S(O)₂N(R¹)—C₀-C₄alkyl-aryl,—N(R¹)-aryl, —CF₃, —N(R¹)—S(O)₂-aryl, fused aryl, fused heterocyclyl,fused cycloalkyl, halo, —N(R¹)C(O)-aryl and —S-aryl, wherein each aryl,heteroaryl, heterocyclyl and cycloalkyl moiety is optionallysubstituted.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, cycloalkyl, alkenyl-aryl,—O—C₀-C₄alkyl-aryl, -alkyl-aryl, —S(O)₂N(R¹)—C₀-C₄alkyl-aryl,—N(R¹)-aryl, —CF₃, —N(R¹)—S(O)₂-aryl, fused aryl, fused heterocyclyl,fused cycloalkyl, halo, —N(R¹)C(O)-aryl and —S-aryl, wherein each aryl,heteroaryl, cycloalkyl and heterocyclyl moiety is optionally substitutedwith 1, 2 or 3 moieties independently selected from the group consistingof phenyl (which itself is optionally substituted with alkyl), halo,alkyl, alkoxy, NO₂, pyrrolyl, thienyl, amino, dialkylamino, morpholinyland —C(NOH)NH₂.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, cycloalkyl, alkenyl-aryl,—O—C₀-C₄alkyl-aryl, -alkyl-aryl, —S(O)₂N(R¹)—C₀-C₄alkyl-aryl,—N(R¹)-aryl, —N(R¹)—S(O)₂-aryl, fused aryl, fused heterocyclyl, fusedcycloalkyl, —N(R¹)C(O)-aryl and —S-aryl, wherein each aryl, heteroaryl,cycloalkyl and heterocyclyl moiety is optionally fused to one or morearyl, heteroaryl or heterocyclyl rings, or one or more saturated orpartially unsaturated cycloalkyl or heterocyclyl rings, each of whichring is optionally substituted.

In another embodiment of the present invention, L is selected from thegroup consisting of phenyl, heteroaryl, cycloalkyl, alkenyl-phenyl,—O—C₀-C₄alkyl-phenyl, -alkyl-phenyl, —S(O)₂N(R¹)—C₀-C₄alkyl-phenyl,—N(R¹)-phenyl, —CF₃, —N(R¹)—S(O)₂-phenyl, fused phenyl, fusedheterocyclyl, fused cycloalkyl, halo, —N(R¹)C(O)-phenyl and —S-phenyl,wherein each phenyl, heteroaryl, cycloalkyl and heterocyclyl moiety isoptionally substituted, wherein said heteroaryl is selected from thegroup consisting of thienyl, pyrrolyl, pyridinyl and furanyl, and eachof which is optionally fused to one or more aryl, heteroaryl orheterocyclyl rings, or one or more saturated or partially unsaturatedcycloalkyl or heterocyclyl rings, each of which ring is optionallysubstituted.

In another embodiment of the present invention, L is selected from thegroup consisting of phenyl, heteroaryl, cycloalkyl, alkenyl-phenyl,—O—C₀-C₄alkyl-phenyl, -alkyl-phenyl, —S(O)₂N(R¹)—C₀-C₄alkyl-phenyl,—N(R¹)-phenyl, —CF₃, —N(R¹)—S(O)₂-phenyl, fused phenyl, fusedheterocyclyl, fused cycloalkyl, halo, —N(R¹)C(O)-phenyl and —S-phenyl,wherein each phenyl, heteroaryl, heterocyclyl and cycloalkyl moiety isoptionally substituted, and wherein said heteroaryl is selected from thegroup consisting of thienyl, pyrrolyl, pyridinyl and furanyl.

In another embodiment of the present invention, L is selected from thegroup consisting of phenyl, heteroaryl, cycloalkyl, alkenyl-phenyl,—O—C₀-C₄alkyl-phenyl, -alkyl-phenyl, —S(O)₂N(R¹)—C₀-C₄alkyl-phenyl,—N(R¹)-phenyl, —CF₃, —N(R¹)—S(O)₂-phenyl, fused phenyl, fusedheterocyclyl, fused cycloalkyl, halo, —N(R¹)C(O)-phenyl and —S-phenyl,wherein said heteroaryl is selected from the group consisting ofthienyl, pyrrolyl, pyridinyl and furanyl and wherein each phenyl,heteroaryl, cycloalkyl and heterocyclyl moiety is optionally substitutedwith 1, 2 or 3 moieties independently selected from the group consistingof phenyl (which itself is optionally substituted with alkyl), halo,alkyl, alkoxy, NO₂, pyrrolyl, thienyl, amino, dialkylamino, morpholinyland —C(NOH)NH₂.

In another embodiment of the present invention, L is selected from thegroup consisting of phenyl, heteroaryl, cycloalkyl, alkenyl-phenyl,—O—C₀-C₄alkyl-phenyl, -alkyl-phenyl, —S(O)₂N(R¹)—C₀-C₄alkyl-phenyl,—N(R¹)-phenyl, —N(R¹)—S(O)₂-phenyl, fused phenyl, fused heterocyclyl,fused cycloalkyl, —N(R¹)C(O)-phenyl and —S-phenyl, wherein saidheteroaryl is selected from the group consisting of thienyl pyrrolyl,pyridinyl and furanyl and wherein each phenyl, heteroaryl, cycloalkyland heterocyclyl moiety is optionally fused to one or more aryl,heteroaryl or heterocyclyl rings, or one or more saturated or partiallyunsaturated cycloalkyl or heterocyclyl rings, each of which ring isoptionally substituted.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, —O—C₀-C₄alkyl-aryl, -alkyl-aryl,—N(R¹)SO₂-aryl, —SO₂N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl, -alkenyl-aryland -alkynyl-aryl, wherein each aryl and heteroaryl group is optionallysubstituted with 1, 2 or 3 independently selected substituents.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, —O—C₀-C₄alkyl-aryl, -alkyl-aryl,—N(R¹)SO₂-aryl, —SO₂N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl, -alkenyl-aryland -alkynyl-aryl, wherein each aryl and heteroaryl group is optionallysubstituted with 1, 2 or 3 substituents independently selected from thegroup consisting of hydroxy, amino, —NH-alkyl, —N(alkyl)₂, —O-alkyl,halo, C₁-C₆alkyl, aryl, heteroaryl, optionally substituted heteroaryl,nitro, cyano, C₂-C₆alkoxy, C₁-C₆alkylamino and CF₃.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, -aryl-aryl, heterocyclyl,-alkynyl-aryl, —O—C₀-C₄alkyl-aryl, -alkyl-aryl,—SO₂—N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl, —O-alkyl-aryl, -heteroaryl-aryland —S-aryl, wherein each aryl, heteroaryl and heterocyclyl moiety isoptionally substituted with 1 to 3 independently selected substituents,and each of which is optionally fused to one or more aryl, heterocyclicor heteroaryl rings, or one or more saturated or partially unsaturatedcycloalkyl or heterocyclyl rings, each of which ring is optionallysubstituted.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, -aryl-aryl, heterocyclyl,-alkynyl-aryl, —O—C₀-C₄alkyl-aryl, -alkyl-aryl,—SO₂—N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl, —O-alkyl-aryl, -heteroaryl-aryland —S-aryl, wherein each aryl, heteroaryl and heterocyclyl moiety isoptionally substituted with 1 to 3 substituents (for example 1 or 2substituents), independently selected from the group consisting ofalkoxy, nitro, halo, alkyl, heterocyclyl and -heteroaryl-alkyl.

In another embodiment of the present invention, L is selected from thegroup consisting of phenyl, thienyl, -phenyl-phenyl, -alkynyl-phenyl,pyrrole, benzo[d]thiazole, —O-phenyl, -alkyl-phenyl, pyridine,—SO₂—NH-alkyl-phenyl, —NH-phenyl, —O-alkyl-phenyl, thienyl-phenyl,pyrrole and —S-phenyl, wherein each aryl, heteroaryl and heterocyclylmoiety is optionally substituted with 1 to 3 independently selectedsubstituents, and each of which is optionally fused to one or more aryl,heterocyclic or heteroaryl rings, or one or more saturated or partiallyunsaturated cycloalkyl or heterocyclyl rings, each of which ring isoptionally substituted.

In another embodiment of the present invention, L is selected from thegroup consisting of phenyl, thienyl, -phenyl-phenyl, -alkynyl-phenyl,pyrrole, benzo[d]thiazole, —O-phenyl, -alkyl-phenyl, pyridine,—SO₂—NH-alkyl-phenyl, —NH-phenyl, —O-alkyl-phenyl, thienyl-phenyl,pyrrole and —S-phenyl, wherein each aryl, heteroaryl and heterocyclylmoiety is optionally substituted with 1 to 3 substituents (for example 1or 2 substituents), independently selected from the group consisting ofalkoxy, nitro, halo, alkyl, heterocyclyl and -heteroaryl-alkyl.

In another embodiment of the present invention, L is aryl or heteroaryl,each of which is optionally substituted with 1, 2 or 3 independentlyselected substituents.

In another embodiment of the present invention, L is phenyl, thienyl orpyridyl, each of which is optionally substituted with 1, 2 or 3independently selected substituents.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, alkoxy, aryl, alkyl, heterocyclyl,heteroaryl, —N(R¹)—C(O)-alkyl-aryl, C(O)—N(R¹)-aryl-O-aryl,—N(R¹)—SO₂-aryl, -alkyl-aryl, -alkyl-heteroaryl, -aryl-heterocyclyl,-heterocyclyl-alkyl-aryl, heterocyclyl-alkyl-heteroaryl,-heterocyclyl-C(O)-aryl, —CH(aryl)₂, -heterocyclyl-C(O)-alkyl,-heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl,-heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,-heterocyclyl-alkyl-heteroaryl, -heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl,-alkyl-O-aryl, -alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R¹)-alkyl-aryl,—C(O)—N(R¹)-aryl, —N(R¹)—C(O)—O-alkyl-aryl, —N(R¹)—SO₂-alkyl-aryl,—N(R¹)—SO₂-aryl and —N(R¹)—SO₂-heteroaryl, wherein each aryl, heteroaryland heterocyclyl moiety is optionally substituted with 1 to 3independently selected substituents, and each of which is optionallyfused to one or more aryl, heterocyclic or heteroaryl rings, or one ormore saturated or partially unsaturated cycloalkyl or heterocyclylrings, each of which ring is optionally substituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, alkoxy, aryl, alkyl, heterocyclyl,heteroaryl, —N(R¹)—C(O)-alkyl-aryl, —C(O)—N(R¹)-aryl-O-aryl,—N(R¹)—SO₂-aryl, -alkyl-aryl, -alkyl-heteroaryl, -aryl-heterocyclyl,-heterocyclyl-alkyl-aryl, heterocyclyl-alkyl-heteroaryl,-heterocyclyl-C(O)-aryl, —CH(aryl)₂, -heterocyclyl-C(O)-alkyl,-heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl,-heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,-heterocyclyl-alkyl-heteroaryl, -heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl,-alkyl-O-aryl, -alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R¹)-alkyl-aryl,—C(O)—N(R¹)-aryl, —N(R¹)—C(O)—O-alkyl-aryl, —N(R¹)—SO₂-alkyl-aryl,—N(R¹)—SO₂-aryl and —N(R¹)—SO₂-heteroaryl, wherein each aryl, heteroaryland heterocyclyl moiety is optionally substituted with 1 to 3substituents independently selected from the group consisting of alkoxy,alkyl, —N(R^(a))(R^(b)), —O-alkyl-heterocyclyl.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, alkoxy, phenyl, —NH—C(O)-alkyl-phenyl, alkyl,halo, thienyl, —C(O)—NH-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine,dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —NH—SO₂-phenyl, -alkyl-phenyl,pyridine, -phenyl-morpholine, benzothiophene, benzo[d][1,3]dioxole,piperidine, -piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl,2,3-dihydrobenzofuran, -piperidine-alkyl-pyridine, —CH(phenyl)₂,-piperidine-C(O)-alkyl, -piperidine-C(O)-pyrrolidine,-piperidine-C(O)—O-alkyl, -piperidine-SO₂-alkyl, -piperidine-SO₂-phenyl,-piperidine-alkyl-indole, -piperidine-SO₂-phenyl-NH—C(O)-alkyl, whereineach aryl, heteroaryl, cycloalkyl and heterocyclyl moiety is optionallysubstituted with 1 to 3 independently selected substituents, and each ofwhich is optionally fused to one or more aryl, heterocyclic orheteroaryl rings, or one or more saturated or partially unsaturatedcycloalkyl or heterocyclyl rings, each of which ring is optionallysubstituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, alkoxy, phenyl, —NH—C(O)-alkyl-phenyl, alkyl,halo, thienyl, —C(O)—NH-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine,dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —NH—SO₂-phenyl, -alkyl-phenyl,pyridine, -phenyl-morpholine, benzothiophene, benzo[d][1,3]dioxole,piperidine, -piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl,2,3-dihydrobenzofuran, -piperidine-alkyl-pyridine, —CH(phenyl)₂,-piperidine-C(O)-alkyl, -piperidine-C(O)-pyrrolidine,-piperidine-C(O)—O-alkyl, -piperidine-SO₂-alkyl, -piperidine-SO₂-phenyl,-piperidine-alkyl-indole, -piperidine-SO₂-phenyl-NH—C(O)-alkyl, whereineach aryl, heteroaryl, cycloalkyl and heterocyclyl moiety is optionallysubstituted with 1 to 3 substituents independently selected from thegroup consisting of alkoxy, alkyl, —N(R^(a))(R^(b)),—O-alkyl-heterocyclyl.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, -aryl-heterocyclyl, -aryl-O—C₀-C₄alkyl,-aryl-O—C₀-C₄alkyl-aryl, —C₁-C₄alkyl, —OR^(e), —C₀-C₃alkyl-aryl,—C₀-C₃alkyl-heteroaryl, —C₀-C₃alkyl-heterocyclyl, aromatic polycycle,non-aromatic polycycle, mixed aromatic and non-aromatic polycycle andfused heterocyclyl, wherein each aryl, heteroaryl, heterocyclyl andpolycycle is optionally substituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, -aryl-heterocyclyl, -aryl-O—C₀-C₄alkyl,-aryl-O—C₀-C₄alkyl-aryl, —C₁-C₄alkyl, —OR^(c), —C₀-C₃alkyl-aryl,—C₀-C₃alkyl-heteroaryl and —C₀-C₃alkyl-heterocyclyl, wherein each aryl,heteroaryl and heterocyclyl is optionally substituted with 1, 2 or 3moieties independently selected from the group consisting of alkoxy,alkyl, fused cycloalkyl, halo and acetyl.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, -aryl-heterocyclyl, -aryl-O—C₀-C₄alkyl,-aryl-O—C₀-C₄alkyl-aryl, —C₁-C₄alkyl, —OR^(e), —C₀-C₃alkyl-aryl,—C₀-C₃alkyl-heteroaryl, —C₀-C₃alkyl-heterocyclyl, aromatic polycyle,non-aromatic polycycle, mixed aromatic and non-aromatic polycycle andfused heterocyclyl, wherein said aryl is a 6-membered aryl group, forexample phenyl, and wherein each aryl, heteroaryl, heterocyclyl andpolycycle is optionally substituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, -aryl-heterocyclyl, -aryl-O—C₀-C₄alkyl,-aryl-O—C₀-C₄alkyl-aryl, —C₁-C₄alkyl, —OR^(e), —C₀-C₃alkyl-aryl,—C₀-C₃alkyl-heteroaryl, —C₀-C₃alkyl-heterocyclyl, aromatic polycyle,non-aromatic polycycle, mixed aromatic and non-aromatic polycycle andfused heterocyclyl, wherein said aryl is a 6-membered aryl group, forexample phenyl, wherein each aryl, heteroaryl, heterocyclyl andpolycycle is optionally substituted with 1, 2 or 3 moietiesindependently selected from the group consisting of alkoxy, alkyl, fusedcycloalkyl, halo and acetyl.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, -aryl-heterocyclyl, -aryl-O—C₀-C₄alkyl,-aryl-O—C₀-C₄alkyl-aryl, —C₁-C₄alkyl, —OR^(e), —C₀-C₃alkyl-aryl,—C₀-C₃alkyl-heteroaryl, —C₀-C₃alkyl-heterocyclyl, aromatic polycyle,non-aromatic polycycle, mixed aromatic and non-aromatic polycycle andfused heterocyclyl, wherein said heteroaryl group is a 5- or 6-memberedheteroaryl group, for example thienyl or pyridinyl, wherein each aryl,heteroaryl, heterocyclyl and polycycle is optionally substituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of H, halo, -aryl-heterocyclyl, -aryl-O—C₀-C₄alkyl,-aryl-O—C₀-C₄alkyl-aryl, —C₁-C₄alkyl, —OR^(e), —C₀-C₃alkyl-aryl,—C₀-C₃alkyl-heteroaryl, —C₀-C₃alkyl-heterocyclyl, aromatic polycyle,non-aromatic polycycle, mixed aromatic and non-aromatic polycycle andfused heterocyclyl, wherein said heteroaryl group is a 5- or 6-memberedheteroaryl group, for example thiophene or pyridine, wherein each aryl,heteroaryl, heterocyclyl and polycycle is optionally substituted with 1,2 or 3 moieties independently selected from the group consisting ofalkoxy, alkyl, fused cycloalkyl, halo and acetyl.

In another embodiment of the present invention, Y is H, aryl (forexample phenyl) or -ayl-heterocyclyl (for example -phenyl-morpholinyl)wherein said aryl and heterocyclyl are optionally substituted.

In another embodiment of the present invention, Y is H, aryl (forexample phenyl) or -ayl-heterocyclyl (for example -phenyl-morpholinyl)wherein said aryl and heterocyclyl are optionally substituted with 1, 2or 3 moieties independently selected from the group consisting ofalkoxy, alkyl, fused cycloalkyl, halo and acetyl.

In another embodiment of the present invention, Y is optionallysubstituted aryl, for example optionally substituted phenyl.

In another embodiment of the present invention, Y is optionallysubstituted aryl, for example optionally substituted phenyl with 1, 2 or3 moieties independently selected from the group consisting of alkoxy,alkyl, fused cycloalkyl, halo and acetyl.

In another embodiment of the present invention, Y is selected from thegroup consisting of —Z¹—Z—Z²-D, —C₀-C₂alkyl-Z—Z³—Z-D, —CH(OR¹)—Z—Z³—Z-D,—C(R¹)(R²)—Z—Z³—Z-D and —C(F)₂—Z—Z³—Z-D, wherein each aryl, heteroaryl,cycloalkyl and heterocyclyl moiety therein is optionally substituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of —Z¹—Z—Z²-D, wherein each aryl, heteroaryl,cycloalkyl and heterocyclyl moiety therein is optionally substituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of —C₀-C₂alkyl-Z—Z³—Z-D, wherein each aryl, heteroaryl,cycloalkyl and heterocyclyl moiety therein is optionally substituted.

In another embodiment of the present invention, Y is selected from thegroup consisting of aromatic polycyle, non-aromatic polycycle, mixedaromatic and non-aromatic polycycle and fused heterocyclyl, each ofwhich is optionally substituted.

In another embodiment of the present invention, each aryl, heterocyclyl,cycloalkyl, and heteroaryl group in Y is optionally substituted with 1,2 or 3 substituents independently selected from the group consisting ofH, halo, OH, —OCH₃, —CN, —S(O)₀₋₂—C₁-C₄alkyl, —CF₃, —OCF₃, alkyl, —NH₂,—N(alkyl)₂, —NH(alkyl), —N(aryl)(alkyl), —N(-alkyl-aryl)(alkyl),—N(heteroaryl)(alkyl), —N(-alkyl-heteroalkylaryl)(alkyl), —NH(aryl),—NH(-alkyl-aryl), —NH(heteroaryl), —NH(-alkyl-heteroalkylaryl),—N(—C₂-C₄alkyl-O-alkyl)(alkyl), —NH(—C₂-C₄alkyl-O-alkyl), —NO₂,—O—C₁-C₄alkyl, —C₀-C₄alkyl-aryl, —C₀-C₄alkyl-heteroaryl,—C₀-C₄alkyl-heterocyclyl, —C₀-C₄alkyl-cycloalkyl, —NHS(O)₂-alkyl,—S(O)₂NH-alkyl, —NR^(a)R^(b), —NR^(c)R^(d), —OR^(e), —OR^(s),—C₂-C₄alkyl-NR^(a)R^(b), C₂-C₄alkyl-NR^(c)R^(d), —S(O)₀₋₂R^(e),—(CR³²R³³)_(s)—NR³⁰R³¹, and (X³⁰—Y³¹—), wherein

-   R³⁰ and R³¹ are each independently hydrogen, cyano, oxo, hydroxyl,    C₁-C₈alkyl, C₁-C₈heteroalkyl, C₁-C₈alkenyl, carboxamido-,    C₁-C₃alkyl-carboxamido-, carboxamido-C₁-C₃alkyl-, amidino-,    C₂-C₈hydroxyalkyl-, C₁-C₃alkyl-aryl-, aryl-C₁-C₃alkyl-,    C₁-C₃alkyl-heteroaryl-, heteroaryl-C₁-C₃alkyl-,    C₁-C₃alkyl-heterocyclyl-, heterocyclyl-C₁-C₃alkyl-,    C₁-C₃alkyl-cycloalkyl-, cycloalkyl-C₁-C₃alkyl-, C₂-C₈alkoxy-,    C₂-C₈alkoxy-C₁-C₄alkyl-, C₁-C₈alkoxy-carbonyl-, aryloxy-carbonyl-,    aryl-C₁-C₃alkoxy-carbonyl-, heteroaryloxy-carbonyl-,    heteroaryl-C₁-C₃alkoxy-carbonyl-, C₁-C₈acyl, C₀-C₈alkyl-carbonyl-,    aryl-C₀-C₈alkyl-carbonyl-, heteroaryl-C₀-C₈alkyl-carbonyl-,    cycloalkyl-C₀-C₈alkyl-carbonyl-, C₀-C₈alkyl-NH-carbonyl-,    aryl-C₀-C₈alkyl-NH-carbonyl-, heteroaryl-C₀-C₈alkyl-NH-carbonyl-,    cycloalkyl-C₀-C₈alkyl-NH-carbonyl-, C₀-C₈alkyl-O-carbonyl-,    aryl-C₀-C₈alkyl-O-carbonyl-, heteroaryl-C₀-C₈alkyl-O-carbonyl-,    cycloalkyl-C₀-C₈alkyl-O-carbonyl-, C₁-C₈alkylsulfonyl-,    aryl-alkyl-sulfonyl-, aryl-sulfonyl-, heteroaryl-alkyl-sulfonyl-,    heteroaryl-sulfonyl-, C₁-C₈alkyl-NH-sulfonyl-,    aryl-alkyl-NH-sulfonyl-, aryl-NH-sulfonyl-,    heteroaryl-alkyl-NH-sulfonyl-, heteroaryl-NH-sulfonyl, aroyl-,    aryl-, cycloalkyl-, heterocyclyl-, heteroaryl-, aryl-C₁-C₃alkyl-,    cycloalkyl-C₁-C₃alkyl-, heterocyclyl-C₁-C₃alkyl-,    heteroaryl-C₁-C₃alkyl-, or protecting group, each of which is    optionally substituted with one or more substituents selected from    halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino and    guanidino, or-   R³⁰ and R³¹ taken together with the N to which they are attached    form a heterocyclyl or heteroaryl, each of which is optionally    substituted with from 1 to 3 substituents selected from the group    consisting of halo, cyano, oxo, carboxy, formyl, nitro, amino,    amidino, guanidino, a protecting group, and (X³⁰—Y³¹—), in which-   X³⁰ is selected from the group consisting of C₁-C₈alkyl-,    C₂-C₈alkenyl-, C₂-C₈alkynyl-, C₀-C₃alkyl-C₂-C₈alkenyl-C₀-C₃alkyl-,    C₀-C₃alkyl-C₂-C₈alkynyl-C₀-C₃alkyl-, C₀-C₃alkyl-O—C₀-C₃alkyl-,    HO—C₀-C₃alkyl-, C₀-C₄alkyl-N(R³⁰)—C₀-C₃alkyl-,    N(R³⁰)(R³¹)—C₀-C₃alkyl-, N(R³⁰)(R³¹)—C₀-C₃alkenyl-,    N(R³⁰)(R³¹)—C₀-C₃alkynyl-, (N(R³⁰)(R³¹))₂—C═N—,    C₀-C₃alkyl-S(O)₀₋₂—C₀-C₃alkyl-, CF₃—C₀-C₃alkyl-,    CF₃—C₀-C₈heteroalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl,    aryl-C₁-C₃alkyl-, cycloalkyl-C₁-C₃alkyl-, heterocyclyl-C₁-C₃alkyl-,    heteroaryl-C₁-C₃alkyl-, N(R³⁰)(R³¹)-heterocyclyl-C₁-C₃alkyl-,    wherein the aryl, cycloalkyl, heteroaryl and heterocycyl are    optionally substituted with from 1 to 3 substituents selected from    halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino and    guanidino; and-   Y³¹ is selected from the group consisting of a direct bond, —O—,    —N(R³⁰)—, —C(O)—, —O—C(O)—, —C(O)—O—, —N(R³⁰)—C(O)—, —C(O)—N(R³⁰)—,    —N(R³⁰)—C(S)—, —C(S)—N(R³⁰)—, —N(R³⁰)—C(O)—N(R³¹)—,    —N(R³⁰)—C(NR³⁰)—N(R³¹)—, —N(R³⁰)—C(NR³¹)—, —C(NR³¹)—N(R³⁰),    —N(R³⁰)—C(S)—N(R³¹)—, —N(R³⁰)—C(O)—O—, —O—C(O)—N(R³¹)—,    —N(R³⁰)—C(S)—O—, —O—C(S)—N(R³¹)—, —S(O)₀₋₂—, —SO₂N(R³¹)—,    —N(R³¹)—SO₂— and —N(R³⁰)—SO₂N(R³¹)—; and-   R³² and R³³ are independently selected from hydrogen, halo and    hydroxyl.

In another embodiment of the present invention, Y is selected from thegroup consisting of aryl, heterocyclyl, cycloalkyl and heteroaryl, eachof which is optionally substituted with 1, 2 or 3 substituents(alternatively 1 or 2 substituents, alternatively 1 substituent)independently selected from the group consisting of H, halo, ═O, OH,C₁-C₃-hydrocarbyl, —OCH₃, —CN, —S(O)₀₋₂—C₁-C₄alkyl, —CF₃, —OCF₃, alkyl,—NH₂, —N(alkyl)₂, —NH(alkyl), —N(aryl)(alkyl), —N(-alkyl-aryl)(alkyl),—N(heteroaryl)(alkyl), —N(-alkyl-heteroalkylaryl)(alkyl), —NH(aryl),—NH(-alkyl-aryl), —NH(heteroaryl), —NH(-alkyl-heteroalkylaryl),—N(—C₂-C₄alkyl-O-alkyl)(alkyl), —NH(—C₂-C₄alkyl-O-alkyl), NO₂,—O—C₁-C₄alkyl, —C₀-C₄alkyl-aryl, —C₀-C₄alkyl-heteroaryl,—C₀-C₄alkyl-heterocyclyl, —C₀-C₄alkyl-cycloalkyl, —NHS(O)₂-alkyl,—S(O)₂NH-alkyl, —NR^(a)R^(b), —NR^(c)R^(d), —OR^(e),—C₂-C₄alkyl-NR^(a)R^(b), C₂-C₄alkyl-NR^(c)R^(d), —S(O)₀₋₁R^(e),—(CR³²R³³)_(s)—N³⁰R³¹, and (X³⁰—Y³¹—),

wherein

-   R³⁰ and R³¹ are each independently hydrogen, cyano, oxo, hydroxyl,    C₁-C₈alkyl, C₁-C₈heteroalkyl, C₁-C₈alkenyl, carboxamido-,    C₁-C₃alkyl-carboxamido-, carboxamido-C₁-C₃alkyl-, amidino-,    C₂-C₈hydroxyalkyl-, C₁-C₃alkyl-aryl-, aryl-C₁-C₃alkyl-,    C₁-C₃alkyl-heteroaryl-, heteroaryl-C₁-C₃alkyl-,    C₁-C₃alkyl-heterocyclyl-, heterocyclyl-C₁-C₃alkyl-,    C₁-C₃alkyl-cycloalkyl-, cycloalkyl-C₁-C₃alkyl-, C₂-C₈alkoxy-,    C₂-C₈alkoxy-C₁-C₄alkyl-, C₁-C₈alkoxy-carbonyl-, aryloxy-carbonyl-,    aryl-C₁-C₃alkoxy-carbonyl-, heteroaryloxy-carbonyl-,    heteroaryl-C₁-C₃alkoxy-carbonyl-, C₁-C₈acyl, C₀-C₈alkyl-carbonyl-,    aryl-C₀-C₈alkyl-carbonyl-, heteroaryl-C₀-C₈alkyl-carbonyl-,    cycloalkyl-C₀-C₈alkyl-carbonyl-, C₀-C₈alkyl-NH-carbonyl-,    aryl-C₀-C₈alkyl-NH-carbonyl-, heteroaryl-C₀-C₈alkyl-NH-carbonyl-,    cycloalkyl-C₀-C₈alkyl-NH-carbonyl-, C₀-C₈alkyl-O-carbonyl-,    aryl-C₀-C₈alkyl-O-carbonyl-, heteroaryl-C₀-C₈alkyl-O-carbonyl-,    cycloalkyl-C₀-C₈alkyl-O-carbonyl-, C₁-C₈alkylsulfonyl-,    aryl-alkyl-sulfonyl-, aryl-sulfonyl-, heteroaryl-alkyl-sulfonyl-,    heteroaryl-sulfonyl-, C₁-C₈alkyl-NH-sulfonyl-,    aryl-alkyl-NH-sulfonyl-, aryl-NH-sulfonyl-,    heteroaryl-alkyl-NH-sulfonyl-, heteroaryl-NH-sulfonyl, aroyl-,    aryl-, cycloalkyl-, heterocyclyl-, heteroaryl-, aryl-C₁-C₃alkyl-,    cycloalkyl-C₁-C₃alkyl-, heterocyclyl-C₁-C₃alkyl-,    heteroaryl-C₁-C₃alkyl-, or protecting group, each of which is    optionally substituted with one or more substituents selected from    halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino and    guanidino, or-   R³⁰ and R³¹ taken together with the N to which they are attached    form a heterocyclyl or heteroaryl, each of which is optionally    substituted with from 1 to 3 substituents selected from the group    consisting of halo, cyano, oxo, carboxy, formyl, nitro, amino,    amidino, guanidino, a protecting group, and (X³⁰—Y³¹—), in which-   X³⁰ is selected from the group consisting of C₁-C₈alkyl-,    C₂-C₈alkenyl-, C₂-C₈alkynyl-, C₀-C₃alkyl-C₂-C₈alkenyl-C₀-C₃alkyl-,    C₀-C₃alkyl-C₂-C₈alkynyl-C₀-C₃alkyl-, C₀-C₃alkyl-O—C₀-C₃alkyl-,    HO—C₀-C₃alkyl-, C₀-C₄alkyl-N(R³⁰)—C₀-C₃alkyl-,    N(R³⁰)(R³¹)—C₀-C₃alkyl-, N(R³⁰)(R³¹)—C₀-C₃alkenyl-,    N(R³⁰)(R³¹)—C₀-C₃alkynyl-, (N(R³⁰)(R³¹))₂—C═N—,    C₀-C₃alkyl-S(O)₀₋₂—C₀-C₃alkyl-, CF₃—C₀-C₃alkyl-, C₁-C₈heteroalkyl,    aryl, cycloalkyl, heterocyclyl, heteroaryl, aryl-C₁-C₃alkyl-,    cycloalkyl-C₁-C₃alkyl-, heterocyclyl-C₁-C₃alkyl-,    heteroaryl-C₁-C₃alkyl-, N(R³⁰)(R³¹)-heterocyclyl-C₁-C₃alkyl-,    wherein the aryl, cycloalkyl, heteroaryl and heterocycyl are    optionally substituted with from 1 to 3 substituents selected from    halo, cyano, oxo, carboxy, formyl, nitro, amino, amidino and    guanidino; and-   Y³¹ is selected from the group consisting of a direct bond, —O—,    —N(R³⁰)—, —C(O)—, —O—C(O)—, —C(O)—O—, —N(R³⁰)—C(O)—, —C(O)—N(R³⁰)—,    —N(R³⁰)—C(S)—, —C(S)—N(R³⁰)—, —N(R³⁰)—C(O)—N(R³¹)—,    —N(R³⁰)—C(NR³⁰)—N(R³¹)—, —N(R³⁰)—C(NR³¹)—, —C(NR³¹)—N(R³⁰),    —N(R³⁰)—C(S)—N(R³¹)—, —N(R³⁰)—C(O)—O—, —O—C(O)—N(R³¹)—,    —N(R³⁰)—C(S)—O—, —O—C(S)—N(R³¹)—, —S(O)₀₋₂—, —SO₂N(R³¹)—,    —N(R³¹)—SO₂— and —N(R³⁰)—SO₂N(R³¹)—; and-   R³² and R³³ are independently selected from hydrogen, halo and    hydroxyl.

In another embodiment of the present invention R^(e) is alkyl.

In another embodiment of the present invention, each aryl, heteroaryl,heterocyclyl, and cycloalkyl moiety of L is optionally substituted withthe group

wherein

is an aryl or heteroaryl;

-   m is an integer from 0 to 3; and-   B² is selected from the group consisting of H, alkyl, aryl,    hereoaryl, halo, —CN, amide, carboxyl, alkoxy, —SO₂NHalkyl, —SO₂NH₂,    —SO₂N(alkyl)₂, —₂NHalkyl-SO, —NH₂SO₂, —N(alkyl)₂SO₂ and haloalkyl,    wherein each aryl, alkyl and heteroaryl moiety is optionally    substituted.

In another embodiment of the present invention, L is selected from thegroup consisting of aryl, heteroaryl, heterocyclyl and cycloalkyl (forexample aryl, for example, phenyl), each of which is optionallysubstituted with the group

wherein

-   B¹ is an aryl or heteroaryl;-   m is an integer from 0 to 3; and-   B² is selected from the group consisting of H, alkyl, aryl,    hereoaryl, halo, —CN, amide, carboxyl, alkoxy, —SO₂NHalkyl, —SO₂NH₂,    —SO₂N(alkyl)₂, —₂NHalkyl-SO, —NH₂SO₂, —N(alkyl)₂SO₂ and haloalkyl,    wherein each aryl, alkyl and heteroaryl moiety is optionally    substituted.

In another embodiment of the present invention,

-   M is —C(O)NHOH;-   n is 1;-   R is H;-   L is aryl or —N(R¹)SO₂-aryl, wherein said aryl moiety is optionally    substituted;-   Y is aryl, alkyl, heteroaryl, or -aryl-C₀-C₃alkyl-heterocyclyl,    wherein said aryl and heteroaryl moieties are optionally    substituted; and-   R¹ is H;    wherein    represents the point of attachment to group M, * represents the    point of attachment to group L and ** represents the point of    attachment to group Y.

In another embodiment of the present invention,

-   M is —C(O)NHOH;-   R is H or —OR¹;-   L is aryl, -aryl-aryl, heteroaryl, —C₂-C₄alkynyl-aryl,    —C₂-C₄alkenyl-aryl, —O—C₀-C₄alkyl-aryl, —C₀-C₄alkyl-aryl,    —NR₁SO₂—C₀-C₄alkyl-aryl, —NR₁-aryl, -aryl-heteroaryl or    -heteroaryl-aryl, wherein each said aryl moiety is optionally    substituted, and optionally fused to one or more aryl or heteroaryl    rings, or one or more saturated or partially unsaturated cycloalkyl    or heterocyclyl rings, each of which ring is optionally substituted,    wherein an aryl moiety in

is optionally connected to an aryl or heteroaryl in L by a bond;

-   Y is H, aryl, heteroaryl or alkyl, wherein said aryl and heteroaryl    moieties are optionally substituted; and-   R¹ is H or alkyl,    wherein    represents the point of attachment to group M, * represents the    point of attachment to group L and ** represents the point of    attachment to group Y.

In another embodiment of the present invention,

-   M is —C(O)NHOH or —C(O)OR¹;-   R is H or —OR¹;-   L is aryl, optionally substituted with

wherein

-   B¹ is aryl;-   m is 1;-   B² is hereoaryl;-   Y is H; and-   R¹ is H or alkyl,    wherein    represents the point of attachment to group M, * represents the    point of attachment to group L and ** represents the point of    attachment to group Y.

In another embodiment of the present invention,

is phenyl, thienyl, thiazolyl, pyrazolyl or oxazolyl;

-   M is —C(O)NHOH;-   L is phenyl, thienyl or pyridine, each of which is optionally    substituted; and-   Y is —Z¹—Z—Z²-D;    wherein-   Z¹ is selected from the group consisting of chemical bond, alkyl,    aryl, heterocyclyl, bridged heterocyclyl, spiro heterocyclyl,    cycloalkyl, heteroaryl, —C(F)R¹—, —C(OR²)R¹—, —C(aryl)R¹—,    —C(heteroaryl)R—, —C(heterocyclyl)R¹—, —C(cycloalkyl)R¹—,    —C(alkyl)R¹—, —C(alkenyl)R¹— and —C(alkynyl)R¹—, wherein each aryl,    heteroaryl, cycloalkyl and heterocyclyl moiety is optionally    substituted and each of which is optionally fused to one or more    aryl or heteroaryl rings, or one or more saturated or partially    unsaturated cycloalkyl or heterocyclyl rings, each of which ring is    optionally substituted;-   Z is selected from the group consisting of chemical bond, —O—,    —NR¹—, —NR^(a)R^(b), —NR^(c)—, —N(C₂-C₄alkyl-OR¹)—, —C(O)—,    —C(NOR¹)—, —CHF—, —CH(CONR¹R²)—CONR¹R²—, —CH(NR¹R²)—CONR¹R²—,    —CH(CONR^(e)R^(f))—CONR¹R²—, —CH(NR^(e)R^(f))—CONR¹R²—,    —CH(heteroaryl) —CONR¹R²—, —CH(heteroaryl-aryl)-CONR¹R²—,    —CH(heteroaryl-heteroaryl)-CONR¹R²—, —C(O)—C(O)NR¹—, —S(O)₀₋₂—,    —NR¹S(O)₂—, —S(O)₂NR¹—, —NR¹S(O)₂NR²—, —NR¹C(O)—, —C(O)NR¹—,    —OC(O)—, —C(O)O—, —NR¹C(NR²)—, —C(NR²)NR¹—, —NR¹C(O)NR²—,    —NR¹C(O)O—, —OC(O)NR¹—, —NR¹C(S)—, —C(S)NR¹—, —NR¹C(S)NR²—,    —NR¹C(S)O—, —OC(S)NR¹—, —O—C₂-C₄alkyl-NR¹—, —NR¹—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-NR^(c)—, —NR^(c)—C₂-C₄alkyl-O—, —O—C₁-C₄alkyl    —S(O)₂NR¹—, —S(O)₂NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹S(O)₂—,    —NR¹S(O)₂—C₁-C₄alkyl-O—, —C(O)—C—C₄alkyl-NR¹—,    —NR¹—C₁-C₄alkyl-C(O)—, —O—C₁-C₄alkyl-C(O)NR¹—,    —C(O)NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹C(O)—,    —NR¹C(O)—C₁-C₄alkyl-O—, —O—C₁-C₄alkyl-C(O)—, —C(O)—C₁-C₄alkyl-O—,    —NR¹—C₁-C₄alkyl-C(O), —C(O)—C₁-C₄alkyl-NR¹—, —O—C₁-C₄alkyl-C(S)—,    —C(S)—C₁-C₄alkyl-O—, —NR¹—C₁-C₄alkyl-C(S), —C(S)—C₁-C₄alkyl-NR¹—,    —NR¹—C₁-C₄alkyl-C(S)—, —O—C₁-C₄alkyl-C(S)NR¹—,    —C(S)NR₁—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹C(S)—,    —NR¹C(S)—C₁-C₄alkyl-O—, —NR¹—C₁-C₄alkyl-S(O)₂—,    —O—C₁-C₄alkyl-S(O)₂NR¹—, —S(O)₂NR¹—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-NR¹S(O)₂—, —NR¹S(O)₂—C₁-C₄alkyl-O—,    —O—C₂-C₄alkyl-OC(O)NR¹— and —O—C₂-C₄alkyl-OC(S)NR¹—;-   Z² is selected from the group consisting of chemical bond, alkyl,    alkenyl, —C(F)R¹—, —C(OR²)R¹—, —C(aryl)R¹—, —C(heteroaryl)R¹—,    —C(heterocyclyl)R¹—, —C(cycloalkyl)R¹—, —C(alkyl)R¹—,    —C(alkenyl)R¹—, —C(alkynyl)R¹—, wherein each alkyl, aryl, alkenyl or    alkynyl moiety is optionally substituted; and-   D is selected from the group consisting of H, aryl, heteroaryl,    alkyl, cycloalyl, heterocyclyl, bridged heterocyclyl, spiro    heterocyclyl, aryl-heterocyclyl, -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -aryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-heteroaryl, each of which is    optionally substituted and each of which is optionally fused to one    or more aryl or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of each    ring is optionally substituted.

In another embodiment of the present invention,

is phenyl, thienyl, benzofuranyl, benzothienyl, thiazolyl, pyrazolyl oroxazolyl;

-   M is —C(O)NHOH;-   L is phenyl, thienyl or pyridine each of which is optionally    substituted; and-   Y is —Z¹—Z—Z²-D;    wherein,-   Z¹ is selected from the group consisting of chemical bond,-   Z is selected from the group consisting of —O—, —NR₁—, —NR^(a)R^(b),    —NR^(c)—, —N(C₂-C₄alkyl-OR)—, —C(O)—, —C(NOR¹)—, —CHF—,    —CH(CONR¹R²)—CONR¹R²—, —CH(NR¹R²)—CONR¹R²—,    —CH(CONR^(e)R^(f))—CONR¹R²—, —CH(NR^(e)R^(f))—CONR¹R²—,    —CH(heteroaryl)-CONR¹R²—, —CH(heteroaryl-aryl)-CONR¹R²—,    —CH(heteroaryl-heteroaryl)-CONR¹R²—, —C(O)—C(O)NR¹—, —S(O)₀₋₂—,    —NR¹S(O)₂—, —S(O)₂NR¹—, —NR¹S(O)₂NR²—, —NR¹C(O)—, —C(O)NR¹—,    —OC(O)—, —C(O)O—, —NR¹C(NR²)—, —C(NR²)NR¹—, —NR¹C(O)NR²—,    —NR¹C(O)O—, —OC(O)NR¹—, —NR¹C(S)—, —C(S)NR¹—, —NR¹C(S)NR²—,    —NR¹C(S)O—, —OC(S)NR¹—, —O—C₂-C₄alkyl-NR¹—, —NR¹—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-NR^(c)—, —NR^(c)—C₂-C₄alkyl-O—, —O—C₁-C₄alkyl    —S(O)₂NR¹—, —S(O)₂NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹S(O)₂—,    —NR¹S(O)₂—C₁-C₄alkyl-O—, —C(O)—C₁-C₄alkyl-NR¹—,    —NR¹—C₁-C₄alkyl-C(O)—, —O—C₁-C₄alkyl-C(O)NR¹—,    —C(O)NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹C(O)—,    —NR¹C(O)—C₁-C₄alkyl-O—, —O—C₁-C₄alkyl-C(O)—, —C(O)—C₁-C₄alkyl-O—,    —NR¹—C₁-C₄alkyl-C(O), —C(O)—C₁-C₄alkyl-NR¹—, —O—C₁-C₄alkyl-C(S)—,    —C(S)—C₁-C₄alkyl-O—, —NR¹—C₁-C₄alkyl-C(S), —C(S)—C₁-C₄alkyl-NR¹—,    —NR¹—C₁-C₄alkyl-C(S)—, —O—C₁-C₄alkyl-C(S)NR¹—,    —C(S)NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹C(S)—,    —NR¹C(S)—C₁-C₄alkyl-O—, —NR¹—C₁-C₄alkyl-S(O)₂—,    —O—C₁-C₄alkyl-S(O)₂NR¹—, —S(O)₂NR¹—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-NR¹S(O)₂—, —NR¹S(O)₂—C₁-C₄alkyl-O—,    —O—C₂-C₄alkyl-OC(O)NR¹—, —O—C₂-C₄alkyl-OC(S)NR¹—;-   Z² is selected from the group consisting of chemical bond, alkyl,    alkenyl, —C(F)R¹—, —C(OR²)R¹—, —C(aryl)R¹—, —C(heteroaryl)R¹—,    —C(heterocyclyl)R¹—, —C(cycloalkyl)R¹—, —C(alkyl)R¹—,    —C(alkenyl)R¹—, —C(alkynyl)R¹—, wherein each alkyl, aryl, alkenyl or    alkynyl moiety is optionally substituted;-   D is selected from the group consisting of H, aryl, heteroaryl,    alkyl, cycloalyl and heterocyclyl, bridged heterocyclyl, spiro    heterocyclyl, aryl-heterocyclyl, -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -aryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-heteroaryl, each of which is    optionally substituted and each of which is optionally fused to one    or more aryl or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of    which ring is optionally substituted.

In another embodiment of the present invention,

is phenyl, thienyl, benzothienyl, benzofuranyl, thiazolyl, pyrazolyl oroxazolyl;

-   M is —C(O)NHOH;-   L is phenyl, thienyl, benzothienyl or pyridine, each of which is    optionally substituted;-   Y is —Z—Z³—Z-D;-   each Z is independently selected from the group consisting of    chemical bond, —O—, —NR¹—, —NR^(a)R^(b), —NR^(c)—,    —N(C₂-C₄alkyl-OR¹)—, —C(O)—, —C(NOR¹)—, —CHF—,    —CH(CONR¹R²)—CONR¹R²—, —CH(NR¹R²)—CONR¹R²—,    —CH(CONR^(e)R^(f))—CONR¹R²—, —CH(NR^(e)R^(f))—CONR¹R²—,    —CH(heteroaryl)-CONR¹R²—, —CH(heteroaryl-aryl)-CONR¹R²—,    —CH(heteroaryl-heteroaryl)-CONR¹R²—, —C(O)—C(O)NR¹—, —S(O)₀₋₂—,    —NR¹S(O)₂—, —S(O)₂NR¹—, —NR¹S(O)₂NR²—, —NR¹C(O)—, —C(O)NR¹—,    —OC(O)—, —C(O)O—, —NR¹C(NR²)—, —C(NR²)NR¹—, —NR¹C(O)NR²—,    —NR¹C(O)O—, —OC(O)NR¹—, —NR¹C(S)—, —C(S)NR¹—, —NR¹C(S)NR²—,    —NR¹C(S)O—, —OC(S)NR¹—, —O—C₂-C₄alkyl-NR¹—, —NR¹—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-NR^(c)—, —NR^(c)—C₂-C₄alkyl-O—, —O—C₁-C₄alkyl    —S(O)₂NR¹—, —S(O)₂NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl —NR¹S(O)₂—,    —NR¹S(O)₂—C₁-C₄alkyl-O—, —C(O)—C₁-C₄alkyl-NR¹—,    —NR¹—C₁-C₄alkyl-C(O)—, —O—C₁-C₄alkyl-C(O)NR¹—,    —C(O)NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹C(O)—,    —NR¹C(O)—C₁-C₄alkyl-O—, —O—C₁-C₄alkyl-C(O)—, —C(O)—C₁-C₄alkyl-O—,    —NR¹—C₁-C₄alkyl-C(O), —C(O)—C₁-C₄alkyl-NR¹—, —O—C₁-C₄alkyl-C(S)—,    —C(S)—C₁-C₄alkyl-O—, —NR¹—C₁-C₄alkyl-C(S), —C(S)—C₁-C₄alkyl-NR¹—,    —NR¹—C₁-C₄alkyl-C(S)—, —O—C₁-C₄alkyl-C(S)NR¹—,    —C(S)NR¹—C₂-C₄alkyl-O—, —O—C₂-C₄alkyl-NR¹C(S)—,    —NR¹C(S)—C₁-C₄alkyl-O—, —NR¹—C₁-C₄alkyl-S(O)₂—,    —O—C₁-C₄alkyl-S(O)₂NR¹—, —S(O)₂NR¹—C₂-C₄alkyl-O—,    —O—C₂-C₄alkyl-NR¹S(O)₂—, —NR¹S(O)₂—C₁-C₄alkyl-O—,-   —O—C₂-C₄alkyl-OC(O)NR¹—, —O—C₂-C₄alkyl-OC(S)NR¹—;-   Z³ is selected from the group consisting of a chemical bond,    C₂-C₅alkyl, aryl, heterocyclyl, bridged heterocyclyl, spiro    heterocyclyl, cycloalkyl and heteroaryl, wherein each aryl,    heteroaryl, cycloalkyl and heterocyclyl moiety is optionally    substituted and each of which is optionally fused to one or more    aryl or heteroaryl rings, or one or more saturated or partially    unsaturated cycloalkyl or heterocyclyl rings, each of which ring is    optionally substituted; and-   D is selected from the group consisting of H, aryl, heteroaryl,    alkyl, cycloalyl and heterocyclyl, bridged heterocyclyl, spiro    heterocyclyl, aryl-heterocyclyl, -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-O—C₀-C₃alkyl-heteroaryl,    -aryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-aryl,    -aryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-heteroaryl,    -heteroaryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-aryl,    -heteroaryl-C₀-C₃alkyl-NR¹—C₀-C₃alkyl-heteroaryl, aromatic    polycycle, non-aromatic polycycle, polyheteroaryl group,    non-aromatic polyheterocyclic and mixed aryl and non-aryl    polyheterocycle, each of which is optionally substituted and each of    which is optionally fused to one or more aryl or heteroaryl rings,    or one or more saturated or partially unsaturated cycloalkyl or    heterocyclyl rings, each of which ring is optionally substituted.

In another embodiment of the present invention,

is aryl or heteroaryl;

-   W is —C═;-   M is —C(O)N(R¹)OR² or —N(OH)C(O)H;-   R¹ and R² are as described for Formula (I);-   n is 0;-   L is selected from the group consisting of aryl, —N(R¹)C(O)-aryl,    —O-alkyl-aryl, —CF₃, heteroaryl, —N(R¹)SO₂-aryl, -alkynyl-aryl,    -alkyl-aryl, —SO₂—N(R¹)-alkyl-aryl, —N(R¹)— alkyl, -aryl-aryl,    —O-aryl, —N(R¹)-aryl, —O-alkyl-aryl, -heteroaryl-aryl,    aryl-heteroaryl and fused heterocycle, wherein said aryl, heteroaryl    and fused heterocycle are optionally substituted;-   Y is selected from the group consisting of H, —OR^(e), aryl, alkyl,    halo, heteroary and -heterocycle-C(O)-alkyl, wherein said aryl and    heteroaryl are optionally substituted; and-   R^(e) is alkyl.

In another embodiment of the present invention,

is aryl or heteroaryl;

-   W is —C═;-   M is —C(O)N(R¹)OR² or —N(OH)C(O)H;-   R¹ and R² are as described for Formula (I);-   n is 0;-   L is selected from the group consisting of aryl, —N(R¹)C(O)-aryl,    —O-alkyl-aryl, —CF₃, heteroaryl, —N(R¹) SO²-aryl, -alkynyl-aryl,    -alkyl-aryl, —SO²—N(R¹)-alkyl-aryl, —N(R¹)-alkyl, -aryl-aryl,    —O-aryl, —N(R¹)-aryl, —O-alkyl-aryl, -heteroaryl-aryl,    aryl-heteroaryl and fused heterocycle, wherein said aryl, heteroaryl    and fused heterocycle are optionally substituted, for example with 1    or 2 substituents independently selected from the group consisting    of halo, phenyl, alkyl, alkoxy, fused heterocycle, NO₂, pyrrolyl,    thienyl and fused phenyl, wherein said phenyl, fused heterocycle,    pryrrolyl, thienyl and fused phenyl are themselves further    optionally substituted with alkyl;-   Y is selected from the group consisting of H, —OR^(e), aryl, alkyl,    halo, heteroaryl and -heterocylce-C(O)-alkyl, wherein said aryl and    heteroaryl are optionally substituted with a substituent selected    from the group consisting of alkyl, alkoxy and fused heterocycle;    and-   R^(e) is alkyl.

In another embodiment of the present invention,

is selected from the group consisting of phenyl, pyrazolyl, thiazolyl,isoxazolyl, thienyl, benzofuranyl, benzothienyl and pyrimidinyl,alternatively phenyl, pyrazolyl, thiazolyl, thienyl and benzothienyl;

-   W is —C═;-   M is —C(O)N(R¹)OR² or —N(OH)C(O)H, for example —C(O)N(R¹)OR²;-   R¹ and R² are as described for Formula (I), alternatively are H or    alkyl;-   n is 0;-   L is selected from the group consisting of phenyl, —N(R¹)C(O)-aryl,    —O-alkyl-aryl, —CF₃, heteroaryl, —N(R¹)—SO₂-aryl, -alkynyl-aryl,    -alkyl-aryl, —SO₂—N(R¹)-alkyl-aryl, —N(R¹)— alkyl, -aryl-aryl,    —O-aryl, —N(R¹)-aryl, -heteroaryl-aryl, —S-aryl and fused    heterocycle, wherein said aryl, heteroaryl and fused heterocycle are    optionally substituted;-   Y is selected from the group consisting of H, —OR^(e), aryl, alkyl,    halo, heteroaryl, —N(R¹)—C(O)-alkyl-aryl, —C(O)—N(R¹)-aryl-O-aryl,    dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one,    —N(R¹)—SO₂-aryl, -alkyl-aryl, -alkyl-O-aryl, -aryl-heterocycle,    benzo[d][1,3]dioxole, heterocycle, -heterocyclyl-alkyl-aryl,    -heterocyclyl-C(O)-aryl, 2,3-dihydrobenzofuan,    -heterocyclyl-alkyl-heteroaryl, —CH-(aryl)₂,    -heterocyclyl-C(O)-heteroaryl, -heterocyclyl-C(O)—O-alkyl,    -heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,    -heterocyclyl-SO₂-aryl-N(R)—C(O)-alkyl,    -alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R¹)-alkyl-aryl,    —C(O)—N(R¹)-aryl, —N(R¹)—C(O)-alkyl-aryl, —N(R¹)—SO₂-aryl,    —N(R¹)—SO₂-alkyl-aryl, —N(R¹)—SO₂-heteroaryl and    -heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl are    optionally substituted; and

R^(e) is alkyl.

In another embodiment of the present invention,

is selected from the group consisting of phenyl, pyrazolyl, thiazolyl,isoxazolyl, thienyl, benzofuranyl, benzothienyl and pyrimidinyl,alternatively phenyl, pyrazolyl, thiazolyl, thienyl and benzothienyl;

-   W is —C═;-   M is —C(O)N(R¹)OR² or —N(OH)C(O)H, for example —C(O)N(R¹)OR²;-   R¹ and R² are as described for Formula (I), alternatively are H or    alkyl;-   n is 0;-   L is selected from the group consisting of phenyl, —N(R¹)C(O)-aryl,    —O-alkyl-aryl, —CF₃, heteroaryl, —N(R¹)—SO₂-aryl, -alkynyl-aryl,    -alkyl-aryl, —SO₂—N(R¹)-alkyl-aryl, —N(R¹)-alkyl, -aryl-aryl,    —O-aryl, —N(R¹)-aryl, -heteroaryl-aryl, —S-aryl and fused    heterocycle, wherein said aryl, heteroaryl and fused heterocycle are    optionally substituted, for example with 1 or 2 substituents    independently selected from the group consisting of halo, phenyl,    alkyl, alkoxy, fused heterocycle, NO₂, pyrrole, thiophene and fused    phenyl, wherein said phenyl, fused heterocycle, pryrrolyl, thienyl    and fused phenyl are themselves further optionally substituted with    alkyl;-   Y is selected from the group consisting of H, —OR^(e), aryl, alkyl,    halo, heteroaryl, —N(R¹)—C(O)-alkyl-aryl, —C(O)—N(R¹)-aryl-O-aryl,    dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one,    —N(R¹)—SO₂-aryl, -alkyl-aryl, -alkyl-O-aryl, -aryl-heterocycle,    benzo[d][1,3]dioxole, heterocycle, -heterocyclyl-alkyl-aryl,    -heterocyclyl-C(O)-aryl, 2,3-dihydrobenzofuan,    -heterocyclyl-alkyl-heteroaryl, —CH-(aryl)₂,    -heterocyclyl-C(O)-heteroaryl, -heterocyclyl-C(O)—O-alkyl,    -heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,    -heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl,    -alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R¹)-alkyl-aryl,    —C(O)—N(R¹)-aryl, —N(R¹)—C(O)-allyl-aryl, —N(R¹)—SO₂-aryl,    —N(R¹)—SO₂-alkyl-aryl, —N(R¹)—SO₂-heteroaryl and    -heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl are    optionally substituted with a substituent selected from the group    consisting of alkyl, alkoxy, —CF₃, optionally substituted phenyl,    —N(R^(a))(R^(b)), —O-alkyl-morpholine and fused heterocycle; and

R^(e) is alkyl.

In another embodiment of the present invention,

is selected from the group consisting of phenyl, pyrazolyl, thiazolyl,isoxazolyl, thienyl, benzofuranyl, benzothienyl and pyrimidinyl,alternatively phenyl, pyrazolyl, thiazolyl, thienyl and benzothienyl;

-   W is —C═;-   M is —C(O)N(R¹)OR² or —N(OH)C(O)H, for example —C(O)N(R¹)OR²;-   R¹ and R² are as described for Formula (I), alternatively are H or    alkyl;-   n is 0;-   L is selected from the group consisting of phenyl,    —N(R¹)C(O)-phenyl, —O-alkyl-phenyl, —CF₃, benzothiazolyl,    —N(R¹)SO₂-phenyl, -alkynyl-phenyl, thienyl, pyrrolyl, -alkyl-phenyl,    pyridine, —SO₂—N(R¹)-alkyl-phenyl, —N(R¹)-alkyl, -phenyl-phenyl,    —O-phenyl, —N(R¹)-aryl, -thienyl-phenyl, —S-phenyl and fused    heterocycle, wherein said phenyl, benzothiazolyl, thienyl, pyrrolyl,    pyridine and fused heterocycle are optionally substituted;-   Y is selected from the group consisting of H, —OR^(e), phenyl,    alkyl, halo, pyrrolyl, thienyl, —N(R¹)—C(O)-alkyl-phenyl,    —C(O)—N(R¹)-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine,    dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R¹)—SO₂-phenyl,    -alkyl-phenyl, -alkyl-O-phenyl, pyridinyl, -phenyl-morpholine,    benzothiophene, benzo[d][1,3]dioxole, piperidinyl,    -piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl,    2,3-dihydrobenzofuan, -piperidine-alkyl-pyridine, —CH-(phenyl)₂,    piperidine-C(O)-pyrrolidine, -piperidine-C(O)—O-alkyl,    -piperidine-SO₂-alkyl, -piperidine-SO₂-phenyl,    -piperidine-alkyl-indole, -piperidine-SO₂-phenyl-N(R¹)—C(O)-alkyl,    -alkyl-O—C(O)—N(R¹)-alkyl-phenyl, -alkyl-N(R¹)-alkyl-phenyl,    —C(O)—N(R¹)-phenyl, —N(R¹)—C(O)-alkyl-phenyl, —N(R¹)—SO₂-phenyl,    —N(R¹)—SO₂-alkyl-phenyl, —N(R¹)—SO₂-thienyl and    -piperidine-C(O)-alkyl, wherein said phenyl, pyrrolyl, pyridinyl,    benzothiophene, piperidinyl, indole and thienyl are optionally    substituted; and

R^(e) is alkyl.

In another embodiment of the present invention,

is selected from the group consisting of phenyl, pyrazolyl, thiazolyl,isoxazolyl, thienyl, benzofuranyl, benzothienyl and pyrimidinyl,alternatively phenyl, pyrazolyl, thiazolyl, thienyl and benzothienyl;

-   W is —C═;-   M is —C(O)N(R¹)OR² or —N(OH)C(O)H, for example —C(O)N(R¹)OR²;-   R¹ and R² are as described for Formula (I), alternatively are H or    alkyl;-   n is 0;-   L is selected from the group consisting of phenyl,    —N(R¹)C(O)-phenyl, —O-alkyl-phenyl, —CF₃, benzothiazolyl,    —N(R¹)SO₂-phenyl, -alkynyl-phenyl, thienyl, pyrrolyl, -alkyl-phenyl,    pyridine, —SO₂—N(R¹)-alkyl-phenyl, —N(R¹)-alkyl, -phenyl-phenyl,    —O-phenyl, —N(R¹)-aryl, -thienyl-phenyl, —S-phenyl and fused    heterocycle, wherein said phenyl, benzothiazolyl, thienyl, pyrrolyl,    pyridine and fused heterocycle are optionally substituted, for    example with 1 or 2 substituents independently selected from the    group consisting of halo, phenyl, alkyl, alkoxy, fused heterocycle,    NO₂, pyrrole, thiophene and fused phenyl, wherein said phenyl, fused    heterocycle, pryrrolyl, thienyl and fused phenyl are themselves    further optionally substituted with alkyl;-   Y is selected from the group consisting of H, —OR^(e), phenyl,    alkyl, halo, pyrrolyl, thienyl, —N(R¹)—C(O)-alkyl-phenyl,    —C(O)—N(R¹)-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine,    dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R¹)—SO₂-phenyl,    -alkyl-phenyl, -alkyl-O-phenyl, pyridinyl, -phenyl-morpholine,    benzothiophene, benzo[d][1,3]dioxole, piperidinyl,    -piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl,    2,3-dihydrobenzofuan, -piperidine-alkyl-pyridine, —CH-(phenyl)₂,    piperidine-C(O)-pyrrolidine, -piperidine-C(O)—O-alkyl,    -piperidine-SO₂-alkyl, -piperidine-SO₂-phenyl,    -piperidine-alkyl-indole, -piperidine-SO₂-phenyl-N(R¹)—C(O)-alkyl,    -alkyl-O—C(O)—N(R¹)-alkyl-phenyl, -alkyl-N(R)-alkyl-phenyl,    —C(O)—N(R¹)-phenyl, —N(R¹)—C(O)-alkyl-phenyl, —N(R¹)—SO₂-phenyl,    —N(R¹)—SO₂-alkyl-phenyl, —N(R¹)—SO₂-thienyl and    -piperidine-C(O)-alkyl, wherein said phenyl, pyrrolyl, pyridinyl,    benzothiophene, piperidinyl, indole and thienyl are optionally    substituted with a substituent selected from the group consisting of    alkyl, alkoxy, —CF₃, optionally substituted phenyl,    —N(R^(a))(R^(b)), —O-alkyl-morpholine and fused heterocycle; and-   R^(e) is alkyl.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ic):

wherein

-   L is selected from the group consisting of aryl, heteroaryl,    -aryl-aryl, -alkynyl-aryl, —O—C₀-C₄alkyl-aryl, -alkyl-aryl,    —SO₂—N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl and -heteroaryl-aryl,    wherein each aryl and heteroaryl moiety is optionally substituted    with 1 to 3 independently selected substituents, and each of which    is optionally fused to one or more aryl, heterocyclic or heteroaryl    rings, or one or more saturated or partially unsaturated cycloalkyl    or heterocyclyl rings, each of which ring is optionally substituted;-   R¹ is selected from the group consisting of —H, -alkyl, -aryl,    -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl,    alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl    moiety is optionally substituted; and-   Y is H, —O-alkyl or optionally substituted aryl.

In another embodiment of the present invention, the invention providescompounds of the Formula (Id):

wherein

-   L is selected from the group consisting of phenyl, thienyl,    -phenyl-phenyl, -alkynyl-phenyl, pyrrole, benzo[d]thiazole,    —O-phenyl, -alkyl-phenyl, pyridine, —SO₂—N(H)—C₀-C₄alkyl-phenyl,    —N(H)-phenyl, —O-alkyl-phenyl and -thienyl-phenyl, wherein each said    phenyl, thienyl, pyrrole, benzo[d]thiazole and pyridine moiety is    optionally substituted with 1 to 3 independently selected    substituents, and each of which is optionally fused to one or more    aryl, heterocyclic or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of    which ring is optionally substituted; and-   Y is H, —O-alkyl or optionally substituted phenyl.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ie):

wherein

-   L is selected from the group consisting of phenyl, thienyl,    -phenyl-phenyl, -alkynyl-phenyl, pyrrole, benzo[d]thiazole,    —O-phenyl, -alkyl-phenyl, pyridine, —SO₂—N(H)—C₀-C₄alkyl-phenyl,    —N(H)-phenyl, —O-alkyl-phenyl and -thienyl-phenyl, wherein each said    phenyl, thienyl, pyrrole, benzo[d]thiazole and pyridine moiety is    optionally substituted with 1 to 3 substituents independently    selected from the group consisting of halo, alkyl, alkoxy, nitro,    pyrrole and fused heterocycle; and-   Y is H, —O-alkyl or optionally substituted phenyl.

In another embodiment of the present invention, the invention providescompounds of the Formula (If):

wherein

-   L is selected from the group consisting of phenyl, thienyl,    -phenyl-phenyl, -alkynyl-phenyl, pyrrole, benzo[d]thiazole,    —O-phenyl, -alkyl-phenyl, pyridine, —SO₂—N(H)—CO—C₄alkyl-phenyl,    —N(H)-phenyl, —O-alkyl-phenyl and -thienyl-phenyl, wherein (1) each    said phenyl moiety is optionally substituted with 1 to 3    substituents independently selected from the group consisting of    halo, alkyl, alkoxy, nitro, pyrrole and fused heterocycle, (2) each    said pyrrole, thienyl and benzo[d]thiazole is substituted with 1 to    2 independently selected alkyl, and (3) said pyridine is substituted    with 1 to 2 independently selected alkoxy; and-   Y is H, —O-alkyl or optionally substituted phenyl.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ig):

wherein

-   L is selected from the group consisting of aryl and heteroaryl,    wherein each aryl and heteroaryl moiety is optionally substituted    with 1 to 3 independently selected substituents, and each of which    is optionally fused to one or more aryl, heterocyclic or heteroaryl    rings, or one or more saturated or partially unsaturated cycloalkyl    or heterocyclyl rings, each of which ring is optionally substituted;    and-   Y is H.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ih):

wherein

-   L is selected from the group consisting of phenyl, pyrrole and    thienyl, each of which is optionally substituted with 1 to 3    independently selected substituents, and each of which is optionally    fused to one or more aryl, heterocyclic or heteroaryl rings, or one    or more saturated or partially unsaturated cycloalkyl or    heterocyclyl rings, each of which ring is optionally substituted;    and-   Y is H.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ii):

wherein

-   L is selected from the group consisting of phenyl, pyrrole and    thienyl, each of which is optionally substituted with 1 to 3    substituents independently selected from the group consisting of    alkoxy, nitro, halo, alkyl, optionally substituted aryl and    optionally substituted heteroaryl; and-   Y is H.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ij):

wherein

-   L is selected from the group consisting of (1) phenyl optionally    substituted with a substituent selected from the group consisting of    alkoxy, nitro, halo and optionally substituted heteroaryl (for    example -thienyl-alkyl), (2) pyrrole and (3) thienyl optionally    substituted with alkyl; and-   Y is H.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ik):

wherein

-   L is aryl or heteroaryl, each of which is optionally substituted;-   Y is selected from the group consisting of aryl, —C₁-C₄alkyl, halo,    heteroaryl, —N(R¹)—C(O)-alkyl-aryl,    —C(O)—N(R¹)—C₀-C₃alkyl-aryl-O-aryl, optionally substituted    dibenzo[b,f][1,4]oxazepine and —N(R¹)S(O)₂-aryl, wherein said aryl    and heteroaryl moieties are optionally substituted; and-   R¹ is selected from the group consisting of —H, -alkyl, -aryl,    -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl,    alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl    moiety is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Il):

wherein

-   L is phenyl or thienyl, each of which is optionally substituted; and-   Y is selected from the group consisting of phenyl, —C₁-C₄alkyl,    halo, thienyl, —N(H)—C(O)-alkyl-phenyl,    —C(O)—N(H)—C₀-C₃alkyl-phenyl-O-phenyl, optionally substituted    dibenzo[b,f][1,4]oxazepine, optionally substituted    dibenzo[b,f][1,4]oxazepine-11-(10H)-one and —N(H)S(O)₂-phenyl,    wherein said phenyl and thienyl moieties are optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Im):

wherein

-   L is phenyl or thienyl, each of which is optionally substituted with    one or more independently selected alkoxy or alkyl; and-   Y is selected from the group consisting of phenyl, —C₁-C₄alkyl,    halo, thienyl, —N(H)—C(O)-alkyl-phenyl,    —C(O)—N(H)—C₀-C₃alkyl-phenyl-O-phenyl, optionally substituted    dibenzo[b,f][1,4]oxazepine, optionally substituted    dibenzo[b,f][1,4]oxazepine-11-(10H)-one and —N(H)S(O)₂-phenyl,    wherein said phenyl and thienyl moieties are optionally substituted    with one or more substituents selected from the group consisting of    alkyoxy, alkyl and optionally substituted phenyl.

In another embodiment of the present invention, the invention providescompounds of the Formula (In):

wherein

-   L is phenyl optionally substituted with alkoxy, or thienyl    optionally substituted with alkyl; and-   Y is selected from the group consisting of phenyl, —C₁-C₄alkyl,    halo, thienyl, —N(H)—C(O)-alkyl-phenyl,    —C(O)—N(H)—C₀-C₃alkyl-phenyl-O-phenyl; optionally substituted    dibenzo[b,f][1,4]oxazepine, optionally substituted    dibenzo[b,f][1,4]oxazepine-11-(10H)-one and —N(H)S(O)₂-phenyl,    wherein said phenyl moieties are optionally substituted with one or    more alkyoxy, and said thienyl moieties are optionally substituted    with alkyl and optionally substituted phenyl (for example phenyl    substituted with amino, alkylamino or dialkylamino).

In another embodiment of the present invention, the invention providescompounds of the Formula (In):

wherein

-   L is optionally substituted aryl; and-   Y is aryl, —C₀-C₃alkyl-aryl or heteroaryl, wherein said aryl and    heteroaryl moieties are optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Io):

wherein

-   L is optionally substituted phenyl; and-   Y is phenyl, —C₀-C₃alkyl-phenyl or pryidinyl, wherein said phenyl    and pyridinyl moieties are optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ip):

wherein

-   L is phenyl optionally substituted with halo; and-   Y is phenyl, —C₀-C₃alkyl-phenyl or pryidinyl, wherein said phenyl    and pyridinyl moieties are optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Iq):

wherein

-   L is optionally substituted aryl; and-   Y is selected from the group consisting of aryl, -aryl-heterocyclyl,    heteroaryl, -heterocyclyl-C₀-C₃alkyl-aryl, —C₀-C₃alkyl-heterocyclyl,    —C(O)-heterocyclyl, -heterocyclyl-C(O)—C₀-C₃alkyl-heterocyclyl,    -heterocyclyl-C(O)O—C₀-C₃alkyl-alkyl,    -heterocyclyl-S(O)₂—C₀-C₃alkyl-alkyl,    -heterocyclyl-S(O)₂—C₀-C₃alkyl-aryl,    -heterocyclyl-C₀-C₃alkyl-heteroaryl,    -heterocyclyl-C(O)—C₀-C₃alkyl-aryl, -heterocyclyl-C(O)-alkyl, and    —CH(aryl)₂, wherein each aryl, heterocyclyl and heteroaryl moiety is    optionally substituted with 1 to 3 independently selected    substituents, and each of which is optionally fused to one or more    aryl, heterocyclic or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of    which ring is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ir):

wherein

-   L is optionally substituted phenyl;-   Y is selected from the group consisting of phenyl,    -phenyl-heterocyclyl, benzothiophene, benzo[d][1,3]dioxole,    piperidine, pyridine, piperidine-alkyl-aryl, piperidine-C(O)-aryl,    2,3-dihydrobenzofuran, thienyl, -piperidine-C₁-C₃alkyl-heterocyclyl,    —CH(phenyl)₂, -piperidine-C(O)-alkyl, -piperidine-C(O)-heterocyclyl,    -piperidine-C(O)—O-alkyl, -piperidine-SO₂-alkyl,    -piperidine-SO₂-aryl, -piperidine-alkyl-heteroaryl,    -piperidine-SO₂-aryl-N(R¹)—C(O)-alkyl, -wherein each of said phenyl,    heterocyclyl, benzothiophene, benzo[d][1,3]dioxole, piperidine,    pyridine, aryl, 2,3-dihydrobenzofuran, thienyl and heteroaryl    moieties is optionally substituted with 1 to 3 independently    selected substituents, and each of which is optionally fused to one    or more aryl, heterocyclic or heteroaryl rings, or one or more    saturated or partially unsaturated cycloalkyl or heterocyclyl rings,    each of which ring is optionally substituted;-   R¹ is selected from the group consisting of —H, -alkyl, -aryl,    -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl,    alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl    moiety is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Is):

wherein

-   L is optionally substituted phenyl; and-   Y is selected from the group consisting of phenyl,    -phenyl-morpholine, benzothiophene, benzo[d][1,3]dioxole,    piperidine, pyridine, piperidine-alkyl-phenyl,    piperidine-C(O)-phenyl, 2,3-dihydrobenzofuran, thienyl,    -piperidine-C₁-C₃alkyl-pyridine, —CH(phenyl)₂,    -piperidine-C(O)-alkyl, -piperidine-C(O)-pyrrolidine,    -piperidine-C(O)—O-alkyl, -piperidine-SO₂-alkyl,    -piperidine-SO₂-phenyl, -piperidine-alkyl-indole and    -piperidine-SO₂-phenyl-N(H)—C(O)-alkyl, wherein each of said phenyl,    morpholine, benzothiphene, benzo[d][1,3]dioxole, piperidine,    pyridine, 2,3-dihydrobenzofuran, pyrrolidine, indole and thienyl    moieties is optionally substituted with 1 to 3 independently    selected substituents, and each of which is optionally fused to one    or more aryl, heterocyclic or heteroaryl rings, or one or more    saturated or partially unsaturated cycloalkyl or heterocyclyl rings,    each of which ring is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (It):

wherein

-   L is phenyl optionally substituted with halo; and-   Y is selected from the group consisting of phenyl,    -phenyl-morpholine, benzothiophene, benzo[d][1,3]dioxole,    piperidine, pyridine, piperidine-alkyl-phenyl,    piperidine-C(O)-phenyl, 2,3-dihydrobenzofuran, thienyl,    -piperidine-C₁-C₃alkyl-pyridine, —CH(phenyl)₂,    -piperidine-C(O)-alkyl, -piperidine-C(O)-pyrrolidine,    -piperidine-C(O)—O-alkyl, -piperidine-SO₂-alkyl,    -piperidine-SO₂-phenyl, -piperidine-alkyl-indole and    -piperidine-SO₂-phenyl-N(H)—C(O)-alkyl, wherein each said phenyl    moiety is optionally substituted with 1 to 3 independently selected    alkoxy or —O-alkyl-heterocyclyl (for example, —O-alkyl-morpholine).

In another embodiment of the present invention, the invention providescompounds of the Formula (Iu):

wherein

-   L is phenyl optionally substituted with halo; and-   Y is optionally substituted piperidine.

In another embodiment of the present invention, the invention providescompounds of the Formula (Iv):

wherein

-   L is optionally substituted phenyl;-   Y is aryl, -alky-O-aryl, —C₀-C₃alkyl-aryl,    -alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R)-alkyl-aryl and    —C(O)—N(R¹)-aryl, wherein each aryl moiety is optionally substituted    with 1 to 3 independently selected substituents, and is optionally    fused to one or more aryl, heterocyclic or heteroaryl rings, or one    or more saturated or partially unsaturated cycloalkyl or    heterocyclyl rings, each of which ring is optionally substituted;    and-   R¹ is selected from the group consisting of —H, -alkyl, -aryl,    -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl,    alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl    moiety is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Iw):

wherein

-   L is optionally substituted phenyl; and-   Y is phenyl, -alky-O-phenyl, —C₀-C₃alkyl-phenyl,    -alkyl-O—C(O)—N(H)-alkyl-phenyl,    -alkyl-O—C(O)—N(alkyl)-alkyl-phenyl, -alkyl-N(H)-alkyl-phenyl,    -alkyl-N(alkyl)-alkyl-phenyl and —C(O)—N(H)-phenyl, wherein each    phenyl moiety is optionally substituted with 1 to 3 independently    selected substituents, and is optionally fused to one or more aryl,    heterocyclic or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of    which ring is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Ix):

wherein

-   L is optionally substituted phenyl;-   Y is selected from the group consisting of H,    —N(R¹)—C(O)—O-alkyl-aryl, —N(R¹)—S(O)₂-aryl, —N(R¹)—S(O)₂-alkyl-aryl    and —N(R¹)—S(O)₂-heteroaryl, wherein each aryl and heteroaryl moiety    is optionally substituted with 1 to 3 independently selected    substituents, and is optionally fused to one or more aryl,    heterocyclic or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of    which ring is optionally substituted; and-   R¹ is selected from the group consisting of —H, -alkyl, -aryl,    -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl,    alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl    moiety is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Iy):

wherein

-   L is optionally substituted phenyl; and-   Y is selected from the group consisting of H,    —N(H)—C(O)—O-alkyl-phenyl, —N(H)—S(O)₂-phenyl,    —N(H)—S(O)₂-alkyl-phenyl and —N(H)—S(O)₂-thiophene, wherein each    phenyl and thiophene moiety is optionally substituted with 1 to 3    independently selected substituents, and is optionally fused to one    or more aryl, heterocyclic or heteroaryl rings, or one or more    saturated or partially unsaturated cycloalkyl or heterocyclyl rings,    each of which ring is optionally substituted.

In another embodiment of the present invention, the invention providescompounds of the Formula (Iz):

wherein

-   L is —S-aryl, aryl or heteroaryl, wherein each aryl and heteroaryl    moiety is optionally substituted with 1 to 3 independently selected    substituents, and is optionally fused to one or more aryl,    heterocyclic or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of    which ring is optionally substituted; and-   Y is optionally substituted aryl.

In another embodiment of the present invention, the invention providescompounds of the Formula (Iaa):

wherein

-   L is —S-phenyl, phenyl or pyridine, wherein each phenyl and pyridine    moiety is optionally substituted with 1 to 3 independently selected    substituents, and is optionally fused to one or more aryl,    heterocyclic or heteroaryl rings, or one or more saturated or    partially unsaturated cycloalkyl or heterocyclyl rings, each of    which ring is optionally substituted; and-   Y is phenyl optionally substituted with halo.

In another aspect of the invention, the invention provides compounds ofthe Formula (II):

-   and N-oxides, hydrates, solvates, pharmaceutically acceptable salts,    prodrugs and complexes thereof, and racemic and scalemic mixtures,    tautomers, diastereomers and enantiomers thereof, wherein-   L² is selected from the group consisting of H, —C₀-C₃alkyl-aryl,    —C₀-C₃alkyl-heteroaryl, —C₁-C₆alkyl, in which each aryl and    heteroaryl is optionally substituted with one, two or three    substituents independently selected from halo, heterocyclyl, CF₃,    amino, OCH₃ and OH; and-   Y and M are defined for Formula (I).

In another embodiment of the present invention, the compound is acompound selected from the group consisting of

  N-hydroxy-2-(thiophen-2-yl)benzamide,N-hydroxy-5-methoxy-2-(thiophen-2-yl)benzamide,4′-fluoro-N-hydroxy-2′-methylbiphenyl-2-carboxamide,N-hydroxy-2′,3′-dimethoxybiphenyl-2-carboxamide,N-hydroxy-2-(phenylethynyl)benzamide,2-(benzo[d][1,3]dioxol-5-yl)-N-hydroxybenzamide,N-hydroxy-3′-methoxybiphenyl-2-carboxamide,4′-fluoro-N-hydroxybiphenyl-2-carboxamide,N-hydroxy-2-(1H-pyrrol-1-yl)benzamide,2-(2,5-dimethyl-1H-pyrrol-1-yl)-N-hydroxybenzamide,N-hydroxy-2′-methoxybiphenyl-2-carboxamide,N-hydroxy-2-(4-methylthiophen-3-yl)benzamide,N-hydroxy-2-(2-methylbenzo[d]thiazol-5-yl)benzamide,2-((4-fluoro-3-methylphenyl)ethynyl)-N-hydroxybenzamide,N-hydroxy-2-phenethylbenzamide,N-hydroxy-3′-nitrobiphenyl-2-carboxamide,N-hydroxy-2-(2-methoxypyridin-3-yl)benzamide,2-(N-benzylsulfamoyl)-N-hydroxybenzamide,3′-fluoro-N-hydroxybiphenyl-2-carboxamide,N-hydroxy-3′-(1H-pyrrol-1-yl)biphenyl-2-carboxamide,N-hydroxydibenzo[b,d]furan-4-carboxamide,N-hydroxy-3′-methoxy-5-methylbiphenyl-2-carboxamide,5-fluoro-N-hydroxy-3′-methoxybiphenyl-2-carboxamide,N-hydroxy-3′-(4-methylthiophen-3-yl)biphenyl-2-carboxamide, ethyl3′-(2-amino-5-(thiophen-2-yl)phenylcarbamoyl)biphenyl- 2-carboxylate,N3′-(2-amino-5-(thiophen-2-yl)phenyl)-N2-hydroxybiphenyl-2,3′-dicarboxamide, 2-(benzyloxy)-N-hydroxybenzamide,N-hydroxy-1,3-diphenyl-1H-pyrazole-4-carboxamide,N-hydroxy-2-(5-phenylthiophen-2-yl)benzamide,N-hydroxy-2,4-bis(4-methylthiophen-3-yl)benzamide,N-hydroxy-2,4-diphenylthiazole-5-carboxamide,N-hydroxy-5-methyl-3-phenylisoxazole-4-carboxamide,N-hydroxy-5-phenyl-3-(phenylsulfonamido)thiophene-2-carboxamide,N-hydroxy-2,5-diphenylthiophene-3-carboxamide,3-(4-bromophenyl)-N-hydroxy-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxamide, (Z)-5-(dibenzo[b,f][1,4]oxazepin-11-yl)-N-hydroxybiphenyl-2-carboxamide,N2-hydroxy-N5-(2-phenoxyphenyl)biphenyl-2,5-dicarboxamide,

1-benzyl-N-hydroxy-3-phenyl-1H-pyrazole-4-carboxamide,1-(4-(benzyloxy)phenyl)-N-hydroxy-3-phenyl-1H-pyrazole- 4-carboxamide,3-(4-fluorophenyl)-N-hydroxy-1-phenyl-1H-pyrazole-4-carboxamide,N-hydroxy-2-(4-morpholinophenyl)-4-phenylthiazole-5-carboxamide,2-(benzo[b]thiophen-3-yl)-N-hydroxy-4-phenylthiazole-5-carboxamide,N-hydroxy-3-phenyl-1-(pyridin-2-yl)-1H-pyrazole-4-carboxamide,N-hydroxy-2,5-diphenyloxazole-4-carboxamide,N-hydroxy-2,5-diphenylthiazole-4-carboxamide,N-hydroxy-4-phenyl-2-(2-phenylacetamido)thiazole-5-carboxamide,N-hydroxy-3-phenylbenzofuran-2-carboxamide,5-(4-dimethylaminophenyl)-N-hydroxybiphenyl-2-carboxamide,N-hydroxy-4-phenyl-2-(piperidin-1-yl)thiazole-5-carboxamide,N²-hydroxy-N⁵-phenylbiphenyl-2,5-dicarboxamide,N-hydroxy-2-phenylbenzofuran-3-carboxamide,N-hydroxy-4-phenyl-2-(pyridin-3-yl)thiazole-5-carboxamide,2-(3,4-dihydroquinolin-1(2H)-yl)-N-hydroxy-4-phenylthiazole-5-carboxamide,N-hydroxy-4-phenyl-2-(pyridin-4-yl)thiazole-5-carboxamide,N⁵-(2-aminophenyl)-N²-hydroxybiphenyl-2,5-dicarboxamide,5-(1H-benzo[d]imidazol-2-yl)-N-hydroxybiphenyl-2-carboxamide,N-hydroxy-5-(phenoxylnethyl)-3-phenylthiophene-2-carboxamide,N-hydroxy-3-phenyl-5-(phenylsulfonamido)benzo[b]thiophene-2-carboxamide,N-hydroxy-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide,3-chloro-N-hydroxy-5-phenylthiophene-2-carboxamide,N²-hydroxy-N⁵-(2-phenoxyphenyl)biphenyl-2,5-dicarboxamide,5-benzyl-N-hydroxy-3-phenylthiophene-2-carboxamide, benzyl2-(hydroxycarbamoyl)-3-phenylbenzo[b]thiophen-5-ylcarbamate,2-(1-benzylpiperidin-4-yl)-N-hydroxy-4-phenylthiazole- 5-carboxamide and2-(1-benzoylpiperidin-4-yl)-N-hydroxy-4-phenylthiazole-5-carboxamide.

Some examples of the compounds according to the first aspect of theinvention are listed in the tables and schemes below. These examplesmerely serve to exemplify some of the compounds of the first aspect ofthe invention and do not limit the scope of the invention.

Synthetic Schemes and Experimental Procedures

The compounds of the invention can be prepared according to the reactionschemes for the examples illustrated below utilizing methods known toone of ordinary skill in the art. These schemes serve to exemplify someprocedures that can be used to make the compounds of the invention. Oneskilled in the art will recognize that other general syntheticprocedures may be used. The compounds of the invention can be preparedfrom starting components that are commercially available. Any kind ofsubstitutions can be made to the starting components to obtain thecompounds of the invention according to procedures that are well knownto those skilled in the art.

Example 1a N-hydroxybiphenyl-2-carboxamide 2N-hydroxybiphenyl-2-carboxamide 2

A solution of 2-biphenylcarboxylic acid 1 (0.25 g, 1.261 mmol), BOP(0.558 g, 1.261 mmol), hydroxylamine hydrochloride (0.088 g, 1.261 mmol)and triethylamine (0.527 mL, 3.78 mmol) was stirred in pyridine (5 mL)at room temperature overnight then diluted with DCM, washed with water(2×), dried over MgSO₄, filtered and solvent evaporated to provide titlecompound 2 (8.8 mg, 3% yield) as a white solid after purification byBiotage (50 to 100% EtOAc in Hexane) followed by trituration (Et₂O). ¹HNMR (400 MHz, DMSO-d₆) δ (ppm): 10.77 (s, 1H), 8.97 (s, 1H), 7.52 to7.42 (m, 1H), 7.40 to 7.33 (m, 8H). LRMS (ESI): (calc.) 213.23 (found)214.2 (MH)+

TABLE 1 Compounds according to Scheme 1. Ex Compound Structure NameCharacterization 1b 3

N- hydroxydibenzo[b, d]furan-4- carboxamide (DMSO-d6) δ (ppm) 1H: 11.11(bs, 1H), 9.33 (bs, 1H), 8.29 (dd, J = 7.6, 1.2 Hz, 1H), 8.20 (dd, J =7.8, 0.6 Hz, 1H), 7.77 (d, J = 5.1 Hz, 1H), 7.75 (dd, J = 5.5, 1.2 Hz,1H), 7.57 (td, J = 7.2, 1.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.44 (td,J = 6.7, 1.2 Hz, 1H). LRMS(ESI): (calc.) 227.22 (found) 228.1 (MH)⁺ 1c 4

N-hydroxy-2- (phenylamino)benz- amide (DMSO-d6) δ (ppm) 1H: 11.24 (s,1H), 9.24 (s, 1H), 9.11 (s, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.34-7.27 (m,4H), 7.13 (dd, J = 8.6, 1.0 Hz, 2H), 6.95 (tt, J = 7.2, 1.0 Hz, 1H),6.81 (td, J = 6.7, 1.8 Hz, 1H). LRMS(ESI): (calc.) 228.25 (found) 229.1(MH)+ 1d 5

2-benzyl-N- hydroxybenzamide (DMSO-d6) δ, (ppm) 1H: 10.93 (s, 1H), 9.09(s, 1H), 7.34 (td, J = 7.4, 2.1 Hz, 1H), 7.27 (td, J = 7.6, 1.6 Hz, 1H),7.25-7.14 (m, 7H), 4.07 (s, 2H). LRMS(ESI): (calc.) 227.26 (found) 228.1(MH)+ 1e 6

2-(benzyloxy)-N- hydroxybenzamide (DMSO-d6) δ, (ppm) 1H: 10.63 (d, J =1.4Hz, 1H), 9.10 (d, J = 1.8 Hz, 1H), 7.50 (dd, J = 7.6, 1.8 Hz, 1H),7.48 (d, J = 7.4 Hz, 2H), 7.42-7.36 (m, 3H), 7.32 (tt, J = 7.2, 1.4 Hz,1H), 7.14 (d, J = 7.8 Hz, 1H), 7.00 (td, J = 7.6, 1.0 Hz, 1H), 5.21 (s,2H). LRMS(ESI): (calc.) 243.26 (found) 244.1 (MH)+

Example 2a N-hydroxy-5-methoxy-2-(thiophen-2-yl)benzamide 11 Step 1:methyl 5-methoxy-2-(thiophen-2-yl)benzoate 10

To a degassed solution of methyl 2-bromo-5-methoxybenzoate 8 (0.25 g,1.020 mmol), 2-thiophene boronic acid 9 (0.170 g, 1.326 mmol),tri-o-tolylphosphine (0.093 g, 0.306 mmol), and K₂CO₃ (0.423 g, 3.06mmol) in DME (3 mL) and water (1 mL) was added Pd(Ph₃P)₄ (0.077 g, 0.066mmol) and the reaction mixture was placed in a preheated oil bath at 85°C. and stirred overnight. The next morning the reaction was complete byHPLC therefore it was solvent evaporated, diluted with DCM, washed withwater, brine, dried over MgSO₄, filtered and solvent evaporated toprovide compound 10 (0.13 g, 52% yield) as a colorless oil afterpurification by Biotage (0 to 10% EtOAc in Hexane). LRMS (ESI): (calc.)248.05 (found) 249.1 (MH)+

Step 2: N-hydroxy-5-methoxy-2-(thiophen-2-yl)benzamide 11

To a stirring solution of methyl 5-methoxy-2-(thiophen-2-yl)benzoate 10(0.13 g, 0.524 mmol) and a solution of 50% hydroxylamine in water (0.53mL, 0.524 mmol) in THF (1 mL) and MeOH (1 mL) was added KOH (0.117 g,2.094 mmol) and the reaction mixture was allowed to stir at roomtemperature for 3 hours. The reaction mixture was solvent evaporated,diluted with DCM, washed with 5% KHSO₄, brine, dried over MgSO₄,filtered and solvent evaporated to provide title compound 11 (50 mg, 38%yield) as a white solid after trituration (overnight, DCM). ¹H NMR (400MHz, DMSO-d₆) δ (ppm): 10.87 (s, 1H), 9.06 (s, 1H), 7.49 (d, J=1.2 Hz,1H), 7.45 (dd, J=15.5, 1.2 Hz, 1H), 7.14 (dd, J=3.5, 1.2 Hz, 1H), 7.05to 7.02 (m, 2H), 6.84 (d, J=2.7 Hz, 1H), 3.78 (s, 3H). LRMS (ESI):(calc.) 249.05 (found) 250.1 (MH)+

TABLE 2 Compounds according to Scheme 2. Ex. Compound Structure NameCharacterization Steps 2b 12

N-hydroxy-2- (thiophen-2- yl)benzamide ¹H NMR (400 MHz, DMSO-d₆) δ(ppm): 10.88 (s, 1H), 9.07 (s, 1H), 7.56 (dd, J = 5.3, 1.2 Hz, 1H), 7.53to 7.50 (m, 1H), 7.46 (dt, J = 7.2, 1.6 Hz, 1H), 7.36 (dt, J = 7.6, 1.6Hz, 1H), 7.31 to 7.29 (m, 1H), 7.25 (dd, J = 3.5, 0.98 Hz, 1H), 7.08(dd, J = 5.1, 3.7 Hz, 1H). LRMS(ESI): (calc.) 219.26 (found) 220.1 (MH)+1 and 2 2c 13

¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 10.81 (d, J = 1.8 Hz, 1H), 9.01 (d, J= 2.0 Hz, 1H), 7.70-7.35 (m, 13H). LRMS(ESI): (calc.) 289.33 (found)290.1 (MH)+ 1 and 2 2d 14

¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 10.82 (s, 1H), 9.00 (s, 1H), 7.71 to7.68 (m, 3H), 7.52 to 7.37 (m, 10H). LRMS(ESI): (calc.) 289.33 (found)290.1 (MH)+ 1 and 2 2e 15

4′-fluoro-N- hydroxy-2′- methylbiphenyl- 2-carboxamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.70 (s, 1H), 8.88 (s, 1H), 7.49-7.43 (m, 1H),7.41-7.38 (m, 2H), 7.16 (d, J = 7.2 Hz, 1H), 7.07 (t, J = 8.4 Hz, 1H),7.05 (dd, J = 10.2, 2.7 Hz, 1H), 6.97 (td, J = 8.6, 2.5 Hz, 1H), 2.04(s, 3H). LRMS(ESI): (calc.) 245.25 (found) 246.1 (MH)+ 1 and 2 2f 16

N-hydroxy-2′,3′- dimethoxybiphenyl- 2-carboxamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.72 (s, 1H), 8.85 (s, 1H), 7.43-7.37 (m, 3H), 7.22(d, J = 7.2 Hz, 1H), 7.12-6.98 (m, 2H), 6.73- 6.72 (m, 1H), 3.48 (s,3H), 3.31 (s, 3H). calc (273.10) MS (m/z): 274.1 (M+30H). 1 and 2 2g 17

¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 10.92 (s, 1H), 9.05 (s, 1H), 7.81(dd, J = 8.1, 2.1 Hz, 1H), 7.74 (dd, J = 7.8, 1.2 Hz, 2H), 7.63 (d, J =2.2 Hz, 1H), 7.53-7.35 (m, 9H). LRMS(ESI): (calc.) 289.33 (found) 290.1(MH)+ 1 and 2 2h 18

2- (benzo[d][1,3]di- oxol-5-yl)-N- hydroxybenzamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.74 (s, 1H), 9.00 (s, 1H), 7.47 (td, J = 7.4, 1.8Hz, 1H), 7.39- 7.32 (m, 3H), 6.95-6.93 (m, 2H), 6.86 (dd, J = 7.9, 1.9Hz, 1H), 6.04 (s, 2H). LRMS(EST): (calc.) 257.07 258.0 (MH)+ 1 and 2 2i19

N-hydroxy-3′- methoxybiphenyl- 2-carboxamide ¹H NMR (400 MHz, DMSO-d₆) δ(ppm): 10.77 (s, 1H), 8.99 (s, 1H), 7.52-7.48 (m, 1H), 7.42-7.39 (m,2H), 7.37 (td, J = 8.0, 1.2 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 6.97 (dd,J = 3.1, 1.0 Hz, 1H), 6.96 (s, 1H), 6.91 (ddd, J = 7.2, 2.5, 1.0 Hz,1H), 3.77 (s, 3H). LRMS(ESI): (calc.) 243.26 244.1 (MH)+ 1 and 2 2j 20

4′-fluoro-N- hydroxybiphenyl- 2-carboxamide ¹H NMR (400 MHz, DMSO-d₆) δ(ppm): 10.79 (s, 1H), 8.99 (s, 1H), 7.51 (td, J = 7.6, 1.6 Hz, 1H),7.44- 7.36 (m, 3H), 7.40 (d, J = 8.4 Hz, 2H), 7.23 (t, J = 9.0 Hz, 2H).LRMS(ESI): (calc.) 231.22 (found) 232.1 (MH)+ 1 and 2 2k 21

N-hydroxy-2- (1H-pyrrol-1- yl)benzamide ¹H NMR (400 MHz, DMSO-d₆) δ(ppm): 10.90 (s, 1H), 9.21 (s, 1H), 7.53 (ddd, J = 9.0, 6.3, 2.7 Hz,1H), 7.41 (d, J = 7.8 Hz, 1H), 7.39 (s, 1H), 7.37 (td, J = 7.6, 1.2 Hz,1H), 6.99 (t, J = 2.2 Hz, 2H), 6.19 (t, J = 2.2 Hz, 2H). LRMS(ESI):(calc.) 202.21 (found) 203.1 (MH)+ 2 2l 22

2-(2,5-dimethyl- 1H-pyrrol-1-yl)- N- hydroxybenzamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.66 (s, 1H), 9.04 (s, 1H), 7.56 (ddd, J = 7.6, 6.7,2.7 Hz, 1H), 7.52-7.48 (m, 2H), 7.16 (dd, J = 7.2, 1.0 Hz, 1H), 5.68 (s,2H), 1.88 (s, 6H). LRMS(ESI): (calc.) 230.26 (found) 231.1 (MH)+ 2 2m 23

N-hydroxy-2′- methoxybiphenyl- 2-carboxamide ¹H NMR (400 MHz, DMSO-d₆) δ(ppm): 10.63 (s, 1H), 8.78 (s, 1H), 7.48-7.44 (m, 1H), 7.39-7.36 (m,2H), 7.31-7.26 (m, 2H), 7.17 (dd, J = 7.4, 1.8 Hz, 1H), 7.00 (d, J = 7.8Hz, 1H), 6.95 (td, J = 7.2, 1.0 Hz, 1H), 3.67 (s, 3H). LRMS(ESI):(calc.) 243.26 (found) 244.1 (MH)+ 1 and 2 2n 24

N-hydroxy-2-(4- methylthiophen- 3-yl)benzamide ¹H NMR (400 MHz, DMSO-d₆)δ (ppm): 10.67 (s, 1H), 8.94 (s, 1H), 7.47-7.39 (m, 3H), 7.26-7.24 (m,2H), 7.17 (s, 1H), 2.04 (s, 3H). LRMS(ESI): (calc.) 233.29 (found) 234.1(MH)+ 1 and 2 2o 25

N-hydroxy-2-(2- methylbenzo[d]- thiazol-5- yl)benzamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.81 (s, 1H), 8.98 (s, 1H), 8.04 (d, J = 8.2 Hz, 1H),7.90 (d, J = 1.8 Hz, 1H), 7.54 to 7.39 (m, 5H), 2.81 (s, 3H). LRMS(ESI):(calc.) 284.33 (found) 285.1 (MH)+ 1 and 2 2p 26

N-hydroxy-3′- nitrobiphenyl-2- carboxamide ¹H NMR (400 MHz, DMSO-d₆) δ(ppm): 10.88 (s, 1H), 9.02 (d, J = 1.6 Hz, 1H), 8.24 to 8.21 (m, 1H),8.19 to 8.18 (m, 2H), 7.83 to 7.81 (m, 1H), 7.73 to 7.69 (m, 1H), 7.60to 7.56 (m, 1H), 7.52 to 7.45 (m, 2H). LRMS(ESI): (calc.) 258.23 (found)259.1 (MH)+ 1 and 2 2q 27

3′-fluoro-N- hydroxybiphenyl- 2-carboxamide ¹H NMR (400 MHz, DMSO-d₆) δ(ppm): 10.82 (s, 1H), 9.03 (s, 1H), 7.53 to 7.51 (m, 1H), 7.47 to 7.36(m, 5H), 7.24 to 7.17 (m, 2H). LRMS(ESI): (calc.) 231.22 (found) 232.1(MH)+ 1 and 2 2r 28

N-hydroxy-3′- (1H-pyrrol-1- yl)biphenyl-2- carboxamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.83 (s, 1H), 9.05 (s, J = 1.6 Hz, 1H), 7.56 to 7.37(m, 9H), 7.26 (d, J = 7.4 Hz, 1H), 6.28 (t, J = 2.2 Hz, 2H). LRMS(ESI):(calc.) 278.31 (found) 279.2 (MH)+ 1 and 2 2s 29

N-hydroxy-3′-(4- methylthiophen- 3-yl)biphenyl-2- carboxamide ¹H NMR(400 MHz, DMSO-d₆) δ (ppm): 10.82 (d, 1H), 9.01 (s, 1H), 7.55 to 7.37(s, 9H), 7.29 to 7.28 (m, 1H), 2.27 (d, J = 0.78 Hz, 3H). LRMS(ESI):(calc.) 309.38 (found) 310.1 (MH)+ 1 and 2 2t 30

N-hydroxy-2-(2- methoxypyridin- 3-yl)benzamide ¹H NMR (400 MHz, DMSO-d₆)δ (ppm): 10.80 (s, 1H), 8.82 (s, 1H), 8.22 (dd, 1H), 7.58 (dd, 1H), 7.50(m, 1H), 7.40 (m, 2H), 7.32 (d, 1H), 7.01 (in, 1H), 3.78 (s, 3H).LRMS(ESI): (calc.) 244.25 (found) 245.1 (MH)+ 1 and 2 2u 31

N-hydroxy-2- phenoxybenzamide ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 10.83(s, 1H), 9.12 (s, 1H), 7.51 (dd, J = 7.4, 1.6 Hz, 1H), 7.44- 7.40 (m,1H), 7.39 (dd, J = 8.6, 7.4 Hz, 2H), 7.19 (td, J = 7.4, 1.0 Hz, 1H),7.14 (tt, J = 7.4, 1.0 Hz, 1H), 7.01 (dd, J = 8.6, 1.0 Hz, 2H), 6.85(dd, J = 8.4, 1.0 Hz, 1H). LRMS(ESI): (calc.) 229.23 (found) 230.1 (MH)+2 2v 32

N-hydroxy-1,3- diphenyl-1H- pyrazole-4- carboxamide ¹H NMR (400 MHz,MeOD-d₆) δ (ppm): 8.54 (s, 1H), 7.84 (d, J = 7.8 Hz, 4H), 7.52 (t, J =7.6 Hz, 2H), 7.45- 7.35 (m, 4H). LRMS(ESI): (calc.) 279.3 (found) 280.3(MH)+ 2 2w 33

N-hydroxy-3′- methoxy-5- methylbiphenyl- 2-carboxamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.70 (s, 1H), 8.95 (s, 1H), 7.25 (m, 4H), 6.95 (m,2H), 6.90 (m, 1H), 3.80 (s, 3H), 2.38 (s, 3H). LRMS(ESI): (calc.) 257.58(found) 258.2 (MH)+ 1 and 2 2x 96

N-hydroxy-2-(5- phenylthiophen- 2-yl)benzamide ¹H NMR (400 MHz, DMSO-d₆)δ (ppm): 10.96 (d, J = 1.4 Hz, 1H), 9.15 (d, J = 1.6 Hz, 1H), 7.68 (dd,J = 8.4, 1.2 Hz, 2H), 7.59 (dd, J = 7.8, 0.8 Hz, 1H), 7.51 (d, J = 3.7Hz, 1H), 7.50 (td, J = 7.8, 1.6 Hz, 1H), 7.44 (t, J = 7.4 Hz, 2H), 7.40(td, J = 7.4, 1.02 Hz, 1H), 7.34 (dd, J = 7.6, 1.4 Hz, 1H), 7.33 (tt, J= 7.4, 1.2 Hz, 1H), 7.27 (d, J = 3.9 Hz, 1H). LRMS(ESI): (calc.) 295.36(found) 296.1 (MH)+ 1 and 2 2y 97

¹H NMR (400 MHz, CD3OD) δ (ppm): 7.39-7.37 (m, 3H), 7.34-7.30 (m, 2H),7.28-7.22 m, 4H), 7.15- (7.10 (m, 4H). LRMS(ESI): (calc.) 289.33 (found)290.2 (MH)+ 1 and 2 2z 98

5-fluoro-N- hydroxy-3′- methoxybiphenyl- 2-carboxamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.80 (s, 1H), 9.05 (s, 1H), 7.42 (m, 1H), 7.28 (m,3H), 6.98 (m, 2H), 6.94 (dd, 1H), 3.78 (s, 3H). LRMS(ESI): (calc.)261.25 (found) 262.1 (MH)+30 1 and 2

Example 3a N-hydroxy-2-(phenylethynyl)benzamide 37 Example 3bN-hydroxy-2-phenethylbenzamide 38 Step 1: methyl2-(phenylethynyl)benzoate 36

To a solution of methyl 2-bromobenzoate 34 (166 μL, 1.163 mmol) inacetonitrile (2906 μL) was added triethylamine (972 μL, 6.98 mmol) andphenylacetylene 35 (140 μL, 1.279 mmol). Then copper (I) iodide (11.07mg, 0.058 mmol), and bis(triphenylphosphine)-palladium(II) chloride(20.40 mg, 0.029 mmol), were successively added, degassing between andafter each addition of catalysts. The mixture was stirred at 75° C.overnight. The reaction mixture was partitioned between EtOAc and 1MHCl. The aqueous layer was extracted with fresh EtOAc and the combinedorganic layers were washed with water, brine, dried over MgSO₄. Theresidue was purified via Biotage using EtOAc/Hex ((0:100 to 10:90); 25+Scolumn), to afford compound 36 (157 mg, 57%). LRMS (ESI): (calc.) 236.08(found) 237.2 (MH)+

Step 2: N-hydroxy-2-(phenylethynyl)benzamide 37

In a 100 mL round-bottomed flask was added methyl2-(phenylethynyl)benzoate 36 (157 mg, 0.665 mmol) in THF (1.33 mL) andMeOH (1.33 mL) and the solution was cooled to 0° C. Then, a 50% aqueoussolution of hydroxylamine (2195 mg, 33.2 mmol) was added followed by a4M aqueous solution of KOH (0.33 mL, 1.329 mmol) and the resultingcolorless solution was stirred at 0° C. and allowed to slowly warm to rtfor 20 h. The reaction mixture was partitioned between EtOAc and H₂O.The aqueous layer was extracted with EtOAc (2×) and the combined organiclayers were washed with brine, dried over MgSO₄, filtered andconcentrated in vacuo. The yellow oil was crystallized in Et₂O and thefiltrate was evaporated and triturated again in Et₂O. The solids werecombined to afford title compound 37 (67 mg, 43% yield) as a whitesolid. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 10.98 (s, 1H), 9.20 (s, 1H),7.61 (d, J=7.4 Hz, 1H), 7.55-7.43 (m, 8H). LRMS (ESI): (calc.) 237.25(found) 238.2 (MH)+

Step 3: N-hydroxy-2-phenethylbenzamide 38

A solution of N-hydroxy-2-(phenylethynyl)benzamide 37 (40 mg, 0.169mmol) in EtOAc (1533 μL) and MeOH (153 μL) was degassed under vacuum andput under N₂ atmosphere (3 cycles). Then a suspension of Pd/C (17.94 g,0.017 mmol) in EtOAc (1 mL) was added and the resulting suspension wasdegassed and put under H₂ atmosphere (3 cycles) and the resulting blacksuspension was stirred at 21° C. for 2 h. The reaction mixture wasfiltered through Celite®. The filtrate was concentrated in vacuo thencrystallized from a mixture of Et₂O and hexane to afford title compound38 (25 mgs, 62% yield) as a white solid. ¹H NMR: (DMSO-d6) δ (ppm):10.90 (s, 1H), 9.10 (s, 1H), 7.37-7.22 (m, 8H), 7.18 (t, J=7.2 Hz, 1H),2.93 (dt, J=9.8, 6.3 Hz, 2H), 2.84 (dt, J=9.7, 5.7 Hz, 2H). LRMS (ESI):(calc.) 241.29 (found) 242.22 (MH)+

TABLE 3 Compounds according to Scheme 3. Ex. Compound Structure NameCharacterization Steps 3c 39

2-((4-fluoro-3- methylphenyl)eth- ynyl)-N- hydroxy- benzamide ¹H NMR(400 MHz, DMSO- d₆) δ (ppm):10.97 (s, 1H), 9.20 (s, 1H), 7.58 (d, J =7.2 Hz, 1H), 7.51-7.44 (m, 4H), 7.39 (ddd, J = 8.4, 5.1, 2.2 Hz, 1H),7.22 (t, J = 9.6 Hz, 1H), 2.25 (s, 3H). LRMS(ESI): (calc.) 269.27(found) 270.1 (MH)+ 1,2,3

Example 4a 2-(N-benzylsulfamoyl)-N-hydroxybenzamide 44 Step 1: methyl2-(N-benzylsulfamoyl)benzoate 43

To a solution of benzylamine 42 (0.140 mL, 1.278 mmol) in DCM (2.557 mL)was added triethylamine (0.535 mL, 3.84 mmol) and methyl2-(chlorosulfonyl)benzoate 41 (300 mg, 1.278 mmol) and the resultingcolorless solution was stirred at rt for 20 h. The reaction mixture waspartitioned between DCM and H₂O. The organic layer was washed with 1MHCl, saturated NaHCO₃, and brine, dried over MgSO₄, filtered andconcentrated. The crude mixture was purified by Biotage using EtOAc/Hex((20:80 to 40:60); 25+S column) to afford compound 43 (49 mgs, 13%yield) as a colorless oil. LRMS (ESI): (calc.) 305.07 (found) 306.2(MH)+

Step 2: 2-(N-benzylsulfamoyl)-N-hydroxybenzamide 44

In a 50 mL round-bottomed flask was added methyl2-(N-benzylsulfamoyl)benzoate 43 (49 mg, 0.160 mmol) in THF (321 μl) andMeOH (321 μl) and the solution was cooled to 0° C. Then, a 50% aqueoussolution of hydroxylamine (530 mg, 8.02 mmol) was added, followed by a4M aqueous solution of KOH (80 μl, 0.321 mmol) and the resultingcolorless solution was stirred at 0° C., allowing to slowly warm to rtand stirred for 18 h. The reaction mixture was partitioned between EtOAcand H₂O. The aqueous layer was extracted with EtOAc and combined organiclayers were washed with brine, dried over MgSO₄, filtered andconcentrated in vacuo to provide a colorless oil. A solid was obtainedby successive dissolution in Et₂O/Hex mixture and concentration whichwas triturated in Et₂O to afford title compound 44 (18 mgs, 37% yield)as a white solid. ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 11.25 (s, 1H), 9.34(s, 1H), 7.83 (dd, J=7.6, 1.2 Hz, 1H), 7.67 (td, J=7.4, 1.4 Hz, 1H),7.61 (td, J=7.6, 1.6 Hz, 1H), 7.50 (dd, J=7.4, 1.6 Hz, 1H), 7.49 (bs,1H), 7.27-7.18 (m, 5H), 4.05 (d, J=5.9 Hz, 2H). LRMS (ESI): (calc.)306.34 (found) 307.14 (MH)+

TABLE 4 Compound according to Scheme 4. Ex. Compound Structure NameCharacterization 4b 45

N-hydroxy-5- phenyl-3- (phenylsulfonamido)- thiophene-2- carboxamide ¹HNMR (400 MHz, DMSO-d₆) δ (ppm): 7.89-7.86 (m, 2H), 7.68- 7.63 (m, 3H),7.60-7.54 (m, 3H), 7.49-7.40 (m, 3H). LRMS(ESI): (calc.) 374.4 (found)375.3 (MH)+

Example 5a Compound 50 Step 1: methyl2,4-bis(trifluoromethylsulfonyloxy)benzoate 47

A solution of methyl 2,4-dihydroxybenzoate 46 (0.5 g, 2.97 mmol),N-phenyltrifluoro-methanesulfonamide (2.125 g, 5.95 mmol) and DIPEA(1.039 mL, 5.95 mmol) in DCM (15 mL) was stirred at room temperature for2 days then washed with saturated NaHCO₃, brine, dried over MgSO₄,filtered and solvent evaporated to provide methyl2,4-bis(trifluoromethylsulfonyloxy)benzoate 47 (1.14 g, 89% yield) afterpurification by Biotage (0 to 10% EtOAc in Hexane). LRMS (ESI): (calc.)431.94 (found) 455.0 (MNa)+

Step 2: Compound 49

To a degassed solution of methyl2,4-bis(trifluoromethylsulfonyloxy)benzoate 47 (0.3 g, 0.694 mmol),3-methoxyphenylboronic acid 48 (0.422 g, 2.78 mmol) and potassiumcarbonate (0.288 g, 2.082 mmol) in toluene (7 mL) was added Pd(Ph₃P)₄(0.241 g, 0.208 mmol). The reaction mixture was stirred at 90° C. for 2h, cooled to rt, diluted with EtOAc, washed with NaHCO₃, brine, driedover Na₂SO₄ and purified by flash chromatography (10% EtOAc/Hex) toafford compound 49 (0.22 g, 91% yield) as a colorless oil.

Step 3: Compound 50

To a solution of compound 49 (0.22 g, 0.631 mmol), in methanol (1.263ml) and THF (1.263 ml) was added potassium hydroxide (0.316 ml, 1.263mmol) followed by the addition of a 50% solution of hydroxylamine inwater (2.086 g, 31.6 mmol). The mixture was stirred at rt for 18 h. Itwas then diluted with H₂O and extracted with EtOAc. The organic phasewas dried over Na₂SO₄ and concentrated. The crude product was purifiedby flash chromatography (5% MeOH/DCM) to afford title compound 50 (46mg, 21% yield) as light brown solid. ¹H NMR (DMSO) d(ppm) 1H, 10.82 (s,1H), 9.01 (s, 1H), 7.69 (dd, 1H), 7.64 (d, 1H), 7.35 (m, 4H), 7.25 (m,1H), 7.60 (m, 2H), 6.95 (m, 2H), 3.82 (s, 3H), 3.78 (s, 3H). LRMS (ESI):(calc.) 349.38 (found) 350.3 (MH)+

TABLE 5 Compounds according to Scheme 5. Ex. Compound Structure NameCharacterization 5b 51

N-hydroxy- 2,4-bis(4- methylthiophen- 3-yl)benzamide ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.72 (s, 1H), 8.98 (s, 1H), 7.58 (d, 1H), 7.45 (m,2H), 7.28 (m, 3H), 7.18 (m, 1H), 2.26 (s, 3H), 2.09 (s, 3H). LRMS (ESI):(calc.) 329.44 (found) 330.1 (MH)+ 5c 52

¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 10.82 (s, 1H), 9.01 (s, 1H), 7.75 (m,2H), 7.70 (dd, 1H), 7.63 9d, 1H), 7.48 (m, 5H), 7.40 (m, 4H). LRMS(ESI): (calc.) 289.33 (found) 290.2 (MH)+

Example 6a ethyl3′-(2-amino-5-(thiophen-2-yl)phenylcarbamoyl)biphenyl-2-carboxylate 62Example 6bN3′-(2-amino-5-(thiophen-2-yl)phenyl)-N2-hydroxybiphenyl-2,3′-dicarboxamide63 Step 1: 3′-tert-butyl 2-ethyl biphenyl-2,3′-dicarboxylate 55

The procedure was followed as outlined in Scheme 2, Step 1 replacingcompounds 8 and 9 with compounds 54 and 53 to afford 3′-tert-butyl2-ethyl biphenyl-2,3′-dicarboxylate 55 (0.2 g, 63% yield) as a lightyellow oil.

Step 2: 2′-(ethoxycarbonyl)biphenyl-3-carboxylic acid 56

To a solution of 3′-tert-butyl 2-ethyl biphenyl-2,3′-dicarboxylate 55(0.2 g, 0.613 mmol) in DCM (2 ml), trifluoroacetic acid (0.472 ml, 6.13mmol) was added and stirred at rt for 5 h. It was then concentrated invacuo, taken up in DCM and concentrated again (2×). The crude compoundwas then dried overnight on the vacuum pump to afford compound 56 (0.166g, 100% yield) as a white solid.

Step 3: tert-butyl 4-bromo-2-nitrophenylcarbamate 58

To a stirring solution of 4-bromo-2-nitroaniline 57 (10.0 g, 46.1 mmol)and di-tert-butyl dicarbonate (20.11 g, 92.2 mmol) in THF (100 mL) wasadded a catalytic amount of DMAP and the reaction mixture was allowed tostir at room temperature for 18 h. The solvent was removed then thecrude di-Boc intermediate (MS: 439/441 (M+Na)) was placed under vacuumthen taken up in THF (46 mL). To this was added a solution of 2N NaOH(46 mL) and the reaction mixture was heated to 70° C. for 4 h. SolidNaOH (1.8 g) was added and the solution was further heated for 18 h thensolvent evaporated to remove the THF and the resulting yellow solid wasfiltered (washed with water) to afford tert-butyl4-bromo-2-nitrophenylcarbamate 58 (15.38 g, >100% yield (not dry)). LRMS(ESI): (calc.) 316.1 (found) 339.0/341.0 (MNa)+

Step 4: tert-butyl 2-nitro-4-(thiophen-2-yl)phenylcarbamate 60

The procedure was followed as outlined in Scheme 2, Step 1 replacingcompound 8 with compound 58 to afford tert-butyl2-nitro-4-(thiophen-2-yl)phenylcarbamate 60 (3.3 g, 77% yield) as ayellow solid. LRMS (ESI): (calc.) 320.08 (found) 343.1 (MNa)+

Step 5: tert-butyl 2-amino-4-(thiophen-2-yl)phenylcarbamate 61

The procedure was followed as outlined in Scheme 3, Step 3 replacingcompound 37 with compound 60 to afford tert-butyl2-amino-4-(thiophen-2-yl)phenylcarbamate 61 (2.75 g, 92% yield) as ayellow solid. LRMS (ESI): (calc.) 290.11 (found) 235.1 (M(−tBu)Na)+

Step 6: ethyl3′-(2-(tert-butoxycarbonylamino)-5-(thiophen-2-yl)phenylcarbamoyl)biphenyl-2-carboxylate62

To a solution of 2′-(ethoxycarbonyl)biphenyl-3-carboxylic acid 56 (0.166g, 0.614 mmol) in pyridine (3 ml), tert-butyl2-amino-4-(thiophen-2-yl)phenylcarbamate 61 (0.4 g, 1.378 mmol) and BOP(0.815 g, 1.843 mmol) were added. The reaction mixture was stirred at rtfor 2 days, concentrated and diluted with DCM then washed with NaHCO₃,brine and dried with Na₂SO₄. Flash purification (5% EtOAc/DCM) affordedthe tert-Boc intermediate (0.333 g, 0.614 mmol) which was taken up inDCM (1.75 mL). Neat trifluoroacetic acid (0.946 mL, 12.28 mmol) wasadded and the reaction mixture was allowed to stir at room temperaturefor 1 h then diluted with DCM and a solution of KOH in brine (0.672 g,in 10 mL brine) and stirred until pH>9. The organic phase was separatedand dried over Na₂SO₄. Flash purification (15% EtOAc/DCM) afforded titlecompound 62 (0.195 g, 72% yield) as a light brown solid. ¹H NMR: (DMSO)d(ppm) 1H, 9.83 (s, 1H), 8.02 (d, 1H), 7.98 (s, 1H), 7.80 (dd, 1H), 7.66(t, 1H), 7.55 (m, 4H), 7.45 (d, 1H), 7.36 (dd, 1H), 7.31 (dd, 1H), 7.24(dd, 1H), 7.05 (dd, 1H), 6.82 (d, 1H), 5.15 (s, 2H), 4.09 (m, 2H), 1.02(t, 3H). LRMS (ESI): (calc.) 442.53 (found) 443.2 (MH)+

Step 7:N3′-(2-amino-5-(thiophen-2-yl)phenyl)-N2-hydroxybiphenyl-2,3′-dicarboxamide63

To a solution of ethyl3′-(2-amino-5-(thiophen-2-yl)phenylcarbamoyl)biphenyl-2-carboxylate 62(0.195 g, 0.441 mmol), in methanol (1.102 ml) and THF (1.102 ml),potassium hydroxide (0.220 ml, 0.881 mmol) was added followed by a 50%hydroxylamine solution in water (1.455 g, 22.03 mmol). The mixture wasstirred at rt for 18 h. It was then diluted with aqueous NaHCO₃, andextracted with EtOAc. The organic phase was dried over Na₂SO₄ andconcentrated. The crude product was purified by flash chromatography(15% MeOH/DCM) to afford title compound 63 (0.04 g, 21% yield) as awhite solid. ¹H NMR: (DMSO) d(ppm) 1H, 10.80 (s, 1H), 9.80 (s, 1H), 9.01(s, 1H), 8.04 (s, 1H), 7.98 (d, 1H), 7.55 (m, 5H), 7.44 (m, 2H), 7.35(d, 1H), 7.30 (dd, 1H), 7.25 (d, 1H), 7.04 (m, 1H), 6.82 (d, 1H), 5.18(s, 2H). LRMS (ESI): (calc.) 429.49 (found) 430.2 (MH)+.

Example 7a3-(4-bromophenyl)-N-hydroxy-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxamide66 Step 1:3-(4-bromophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxylic acid 65

Procedure involves adding first KOH (0.177 g, 3.15 mmol) and thenpotassium permanganate (0.498 g, 3.15 mmol) to a suspension of aldehyde64 (0.750 g, 2.1 mmol) in dioxane/water (8.5/2.1 mLs). The resultingsolution was stirred at r.t. for 1 h prior to dilution with aq. HCluntil pH=1, and extraction with EtOAc. The combined organic extractswere dried with anhydrous Na₂SO₄, filtered, and concentrated. Theresidue was taken up in EtOAc, and triturated with hexanes to affordcompound 65 (0.622 g, 79% yield) as a white solid which was collected byfiltration. LRMS (ESI): (calc.) 372.01 (found) 375.2 (MH)+

Step 2:3-(4-bromophenyl)-N-hydroxy-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxamide66

A solution of3-(4-bromophenyl)-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxylic acid 65(0.30 g, 0.804 mmol), hydroxylamine hydrochloride (0.112 g, 1.608 mmol),BOP (0.427 g, 0.965 mmol) and triethylamine (0.336 mLs, 2.412 mmol) inpyridine (10 mLs) was stirred at room temperature for 2 h. All solventswere then removed under reduced pressure, and the residue diluted withbrine and aq. HCl until pH=1. Following extraction with EtOAc, thecombined organic extracts were dried with anhydrous Na₂SO₄, filtered,and concentrated. The residue was purified by column chromatography onsilica gel using 50-100% EtOAc/hexanes as the eluent to afford titlecompound 66 (10 mgs, 3% yield) as a light orange solid.

¹H NMR: (MeOD-d4) 8.46 (s, 1H), 7.84-7.73 (m, 4H), 7.64-7.57 (m, 2H),7.13-7.06 (m, 2H), 3.89 (s, 3H). LRMS (ESI): (calc.) 388.2 (found)386.1/388.1 (MH)−

Example 8a N-hydroxy-2,5-diphenylthiophene-3-carboxamide 71 Step 1:ethyl 2-benzoyl-4-oxo-4-phenylbutanoate 69

To a stirring solution of ethyl 3-oxo-3-phenylpropanoate 67 (0.754 g,3.92 mmol) in THF cooled to 0° C. was added potassium tert-butoxide(0.556 g, 4.71 mmol) and the reaction mixture was stirred for 10 minutesfollowed by the addition of 2-bromo-1-phenylethanone 68 (0.859 g, 4.32mmol). The reaction mixture was allowed to stir at room temperature for90 minutes then quenched with ethanol (2 mL) and poured into ethylacetate and layer separated. The organic layer was washed with water,brine, dried over Na₂SO₄, then purified by ISCO (40 g column, 0 to 35%ethyl acetate in hexane) to afford compound 69 (0.812 g, 67% yield) as ayellow oil. LRMS (ESI): (calc.) 310.12 (found) 311.08 (MH)+

Step 2: ethyl 2,5-diphenylthiophene-3-carboxylate 70

To a stirring solution of ethyl 2-benzoyl-4-oxo-4-phenylbutanoate 69(0.812 g, 2.62 mmol) in toluene (20 mLs) was added Lawesson's reagent(1.270 g, 3.14 mmol) and the reaction mixture was refluxed for 4 h thenconcentrated. The crude residue was purified by ISCO (40 g column, 0 to30% ethyl acetate in hexane) to afford ethyl2,5-diphenylthiophene-3-carboxylate 70 (0.44 g 55% yield) as a yellowoil. LRMS (ESI): (calc.) 308.09 (found) 309.27 (MI-1H)+

Step 3: N-hydroxy-2,5-diphenylthiophene-3-carboxamide 71

To a stirring solution of ethyl 2,5-diphenylthiophene-3-carboxylate 70(0.440 g, 1.427 mmol) in methanol (7 mL) and THF (7 mL) was added 50%hydroxylamine in water (1.4 mL, 23.31 mmol) and the resulting mixturewas stirred at room temperature for 45 minutes then concentrated to onethird volume. The solution was neutralized with 3N HCl to pH 7 and thedesired product was filtered then purified by Gilson (55 to 95% MeOH inH₂O) to afford the title compound 71 (87 mg, 21% yield) as a whitesolid. ¹H NMR: (DMSO-d6) d(ppm) 1H, 10.96 (s, 1H), 9.14 (s, 1H),7.71-7.69 (m, 2H), 7.57-7.55 (m, 3H), 7.48-7.34 (m, 6H) LRMS (ESI):(calc) 295.36 (found) 296.22 (MH)+

Example 9a N-hydroxy-2,4-diphenylthiazole-5-carboxamide 74 Step 1:methyl 2,4-diphenylthiazole-5-carboxylate 73

To a pre-cooled (0° C.) solution of2,4-Diphenyl-1,3-thiazole-5-carboxylic acid 72 (400 mg, 1.422 mmol) inEtOAc (7.109 ml) was added a 0.5 M solution of diazomethane (5.69 ml,2.84 mmol) in Et₂O (freshly prepared) (c.a. 5 mL) and the resultingwhite suspension was stirred at 0° C. for 1 h. TLC showed completion.Then, the small amount of white solid left was filtered off and thefiltrate was concentrated in vacuo to afford methyl2,4-diphenylthiazole-5-carboxylate 73 (0.449 g, 107% yield).

Step 2: N-hydroxy-2,4-diphenylthiazole-5-carboxamide 74

A 100 mL round-bottomed flask was charged with methyl2,4-diphenylthiazole-5-carboxylate 73 (420 mg, 1.422 mmol) in MeOH(2.844 ml) and THF (2.84 ml) and the solution was cooled down to 0° C.Then a 50% aqueous solution of hydroxylamine (4697 mg, 71.1 mmol) and 4Mpotassium hydroxide solution (0.427 ml, 1.706 mmol) were added and thereaction mixture was allowed to warm up to rt while stirring for 18 h.The reaction mixture was partitioned between EtOAc and water. Theaqueous layer was extracted with fresh EtOAc and the combined organiclayers were washed with 1M HCl, sat NaHCO₃, and brine, dried over MgSO₄,filtered and concentrated. The resulting solid was triturated (Et₂O) toafford the title compound 74 (0.303 g, 72% yield). ¹H NMR: (DMSO-d6)d(ppm) 1H, 11.29 (s, 1H), 9.44 (s, 1H), 8.03 (dd, J=6.3, 2.7 Hz, 2H),7.84 (d, J=7.0 Hz, 2H), 7.56-7.55 (m, 3H), 7.50-7.43 (m, 3H). LRMS(ESI): (calc.) 296.34 (found) 297.1 (MH)+

TABLE 6 Compound according to Scheme 9. Ex Compound Structure NameCharacterization 9b 75

N-hydroxy-5- methyl-3- phenylisoxazole- 4-carboxamide ¹H NMR (400 MHz,CD3OD) δ (ppm): 7.47-7.45 (m, 2H), 7.34-7.29 (m, 3H), 2.55 (s, 3H) LRMS(ESI): (calc.) 218.0 (found) 219.0 (MH)+

Example 10a4-(4-fluorophenyl)-N-hydroxy-2-(4-methoxyphenyl)thiazole-5-carboxamide80 Step 1: methyl 2-bromo-3-(4-fluorophenyl)-3-oxopropanoate 78

To a solution of methyl 3-(4-fluorophenyl)-3-oxopropanoate 76 (1 equiv,500 mg, 2.55 mmol) in DCM (17 mL) was added a solution of bromine (1.3equiv, 530 mg, 3.31 mmol) in DCM (1.5 mL) in a drop wise manner at 0° C.The reaction mixture was stirred further for an additional 1 h and thentreated with 10% aqueous K₂CO₃ (5 mL) solution. The organic phase wasseparated, dried over Na₂SO₄, filtered and concentrated under reducedpressure to afford methyl 2-bromo-3-(4-fluorophenyl)-3-oxopropanoate 78(700 mg, 100% yield). LRMS (ESI):(calc) 273.96 (found) 275.108 (MH)+.

Step 2: methyl4-(4-fluorophenyl)-2-(4-methoxyphenyl)thiazole-5-carboxylate 79

To a stirring solution of methyl2-bromo-3-(4-fluorophenyl)-3-oxopropanoate 78 (1 equiv, 1.15 g, 4.2mmol) in MeCN at room temperature was added 4-methoxybenzo-thioamide 77(1 equiv, 700 mg, 4.2 mmol) and the reaction mixture was stirred for 18h. The solvent was evaporated and the residue purified by triturationwith diethyl ether to afford methyl4-(4-fluorophenyl)-2-(4-methoxyphenyl)thiazole-5-carboxylate 79 (320 mg,22% yield). LRMS (ESI): (calc) 343.37 (found) 344.235 (MH)+.

Step 3:4-(4-fluorophenyl)-N-hydroxy-2-(4-methoxyphenyl)thiazole-5-carboxamide80

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 79 to afford title compound4-(4-fluorophenyl)-N-hydroxy-2-(4-methoxyphenyl)thiazole-5-carboxamide80 (86% yield) after overnight trituration in water. ¹H NMR (400 MHz,CD3OD) δ (ppm): 7.95 (d, J=8.8 Hz, 2H), 7.85 (m, 2H), 7.18 (t, J=8.8,Hz, 2H), 7.04 (d, 8.8 Hz, 2H), 3.87 (s, 3H). LRMS (ESI): (calc) 344.36(found) 345.2 (MH)+.

TABLE 6 Compounds according to Scheme 10 Ex Compound Structure NameCharacterization 10b 81

2-(benzo[d][1,3]- dioxol-5-yl)-N- hydroxy-4- phenylthiazole-5-carboxamide (CD3OD) δ (ppm) 1H: 7.85 (d, J = 7.2 Hz, 2H), 7.53 (m, 2H),7.44-7.34 (m, 3H), 6.92 (d, J = 8.0 Hz, 1H), 6.05 (s, 2H) LRMS (ESI):(calc.) 340.0 (found) 341.2 (MH)+

Example 11a N-hydroxy-3,5-diphenylthiophene-2-carboxamide 86 Step 1:methyl 3-chloro-5-phenylthiophene-2-carboxylate 83

To a stirring solution of methyl 3-amino-5-phenylthiophene-2-carboxylate82 (1.166 g, 5 mmol) in water (14 mL) and concentrated hydrochloric acid(7 mL) cooled to 0° C. was added a solution of sodium nitrite (0.431 g,6.25 mmol) in water (2 mL). The reaction mixture was stirred for 30 minthen the resulting solution was poured into a solution of CuCl (1.732 g,17.50 mmol) in concentrated hydrochloric acid (20 mL) still at 0° C. Thereaction was allowed to slowly warm to room temperature over 4 h thenpoured into ice cold water and extracted with ether (3×). The combinedorganic phases were washed with water, dried over Na₂SO₄, filtered andconcentrated under reduced pressure to afford methyl3-chloro-5-phenylthiophene-2-carboxylate 83 as a white solid (0.850 mg,67% yield) after purification by ISCO (40 g column, 5 to 40% ethylacetate in hexane). LRMS (ESI): (calc) 252.72 (found) 253.06 (MH)+

Step 2: methyl 3,5-diphenylthiophene-2-carboxylate 85

The procedure was followed as outlined in Scheme 2, Step 1 replacingcompounds 8 and 9 with compounds 83 and 84 to afford methyl3,5-diphenylthiophene-2-carboxylate 85 (90% yield) as a white solidafter purification by ISCO (12 g column, 0 to 30% ethyl acetate inhexane). LRMS (ESI): (calc) 294.37 (found) 295.21 (MH)+

Step 3: N-hydroxy-3,5-diphenylthiophene-2-carboxamide 86

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 85 to afford title compoundN-hydroxy-3,5-diphenylthiophene-2-carboxamide 86 (21% yield) as a whitesolid after purification by Gilson (60 to 95% MeOH in water). ¹H NMR(400 MHz, DMSO-d₆) δ (ppm): 10.96 (s, 1H), 9.22 (s, 1H), 7.76-7.74 (m,2H), 7.70 (s, 1H), 7.57-7.54 (m, 2H), 7.48-7.34 (m, 6H). LRMS (ESI):(calc) 295.36 (found) 296.19 (MH)+

Example 12a N-hydroxy-3,5-diphenylthiophene-2-carboxamide 89 Step 1:methyl 3-phenylbenzo[b]thiophene-2-carboxylate 88

To a stirring solution of (2-fluorophenyl)(phenyl)methanone 87 (2 g,9.99 mmol) and methyl 2-mercaptoacetate in DMF (30 mL) was addedpotassium carbonate (4.14 g, 30.0 mmol) and the reaction mixture wasstirred at 70° C. for 16 h. The solvent was removed under reducedpressure and the resulting residue was diluted with ethyl acetate andwashed with water. The organic layer was dried over Na₂SO₄, filtered andconcentrated under reduced pressure to afford methyl3-phenylbenzo[b]thiophene-2-carboxylate 88 as a white oily solid (0.62g, 23% yield) after purification by ISCO (0 to 40% ethyl acetate inhexane). LRMS (ESI): (calc) 268.33 (found) 269.156 (MH)+

Step 2: N-hydroxy-3,5-diphenylthiophene-2-carboxamide 89

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 88 to afford title compoundN-hydroxy-3,5-diphenylthiophene-2-carboxamide 89 (10% yield) as a whitesolid after purification by ISCO (0 to 100% Ethyl acetate in hexane)followed by recrystallization from MeCN and water. ¹H NMR (400 MHz,DMSO-d₆) δ (ppm): 10.85 (br s, 1H), 9.22 (br s, 1H), 8.08 (d, J=7.8 Hz,1H), 7.58-7.41 (m, 8H). LRMS (ESI): (calc) 269.32 (found) 270.1 (MH)+.

Example 13a N-hydroxy-3,5-diphenylthiophene-2-carboxamide 92 Step 1:ethyl 2-(1-acetylpiperidin-4-yl)-4-phenylthiazole-5-carboxylate 91

To prepare compound 90, the procedure was followed as outlined in Scheme10, Step 2 replacing compounds 77 and 78 with compounds tert-butyl4-carbamothioylpiperidine-1-carboxylate and ethyl2-bromo-3-oxo-3-phenylpropanoate to afford compound 90 (0.790 g, 21%yield) as a white solid. To a stirring solution of ethyl4-phenyl-2-(piperidin-4-yl)thiazole-5-carboxylate 90 (0.235 g, 0.743mmol) in THF (8 mL) was added acetyl chloride (1.11 mL, 0.891 mmol) andthe reaction was stirred at room temperature for 2 h. The solution wasdiluted with brine and extracted with ethyl acetate. The combinedorganics were dried over Na₂SO₄, filtered and concentrated under reducedpressure to afford ethyl2-(1-acetylpiperidin-4-yl)-4-phenylthiazole-5-carboxylate 91 as a lightyellow oil (0.196 g, 74% yield) after purification by flashchromatography (0 to 10% MeOH in ethyl acetate). LRMS (ESI): (calc)358.45 (found) 359.3 (MH)+

Step 2: N-hydroxy-3,5-diphenylthiophene-2-carboxamide 92

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 91 to afford title compoundN-hydroxy-3,5-diphenylthiophene-2-carboxamide 92 (20% yield) as a beigesolid after purification by flash chromatography (0 to 30% MeOH in ethylacetate). ¹H NMR (400 MHz, CD3OD) δ (ppm): 7.82-7.73 (m, 2H), 7.50-7.38(m, 3H), 4.60 (d, J=13.3 Hz, 1H), 4.05 (d, J=13.3 Hz, 1H), 3.44-3.29 (m,2H), 2.94-2.83 (m, 1H), 2.28-2.14 (m, 5H), 1.94-1.68 (m, 2H). LRMS(ESI): (calc) 345.42 (found) 346.3 (MH)+

Example 14a N-hydroxy-3,6-diphenylimidazo[2,1-b]thiazole-2-carboxamide95 Step 1: ethyl 3,6-diphenylimidazo[2,1-b]thiazole-2-carboxylate 94

A solution of ethyl 2-amino-4-phenylthiazole-5-carboxylate 93 (0.7 g,2.82 mmol) and 3-(2-bromoacetyl)benzene-1-ylium 68 (0.34 mL, 2.82 mmol)was stirred at 120° C. in butanol (9 mL) for 3 d. The solution wascooled to room temperature, diluted with brine and extracted with ethylacetate. The combined organics were dried over Na₂SO₄, filtered andconcentrated under reduced pressure to afford ethyl3,6-diphenylimidazo[2,1-b]thiazole-2-carboxylate 94 (0.18 g, 18% yield)as a tan solid after purification by flash chromatography (0 to 30% MeOHin ethyl acetate) followed by trituration in hexane. LRMS (ESI): (calc)348.42 (found) 349.2 (MH)+

Step 2: N-hydroxy-3,6-diphenylimidazo[2,1-b]thiazole-2-carboxamide 95

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 94 to afford title compoundN-hydroxy-3,6-diphenylimidazo[2,1-b]thiazole-2-carboxamide 95 (83%yield) as a beige solid after purification by trituration (ethyl acetateand hexane). ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 8.20 (br s, 1H),7.97-7.92 (m, 2H), 7.76-7.70 (m, 2H), 7.67-7.61 (m, 3H), 7.45-7.39 (m,2H), 7.34-7.28 (m, 1H) LRMS (ESI):(calc) 335.4 (found) 336.3 (MH)+.

Example 15a(Z)-5-(dibenzo[b,f][1,4]oxazepin-11-yl)-N-hydroxybiphenyl-2-carboxamide104 Step 1: methyl 2-iodo-4-(2-phenoxyphenylcarbamoyl)benzoate 101

To a stirring solution of 2-phenoxyaniline 99 (0.813 g, 4.39 mmol) and3-iodo-4-(methoxycarbonyl)benzoic acid 100 (1.28 g, 4.18 mmol) in DMF(15 mL) was added BOP (1.942 g, 4.39 mmol) and TEA (1.166 mL, 8.36mmol), the reaction mixture was stirred at room temperature for 1 h thenpoured into water. The desired product was extracted with ethyl acetateand the combined organic layers were washed with water, brine, driedover Na₂SO₄, filtered and solvent evaporated to provide methyl2-iodo-4-(2-phenoxyphenylcarbamoyl)benzoate 101 (1.382 g, 70% yield) asa red foam after purification by flash chromatography (0 to 40% ethylacetate in hexane).

LRMS (ESI): (calc.) 473.26 (found) 474.21 (MH)+

Step 2: methyl 5-(2-phenoxyphenylcarbamoyl)biphenyl-2-carboxylate 102

The procedure was followed as outlined in Scheme 2, Step 1 replacingcompounds 8 and 9 with compounds 101 and 84 to afford5-(2-phenoxyphenylcarbamoyl)biphenyl-2-carboxylate 102 (1.07 g, 87%yield) as an orange foam after purification by ISCO (40 g column, 0 to40% ethyl acetate in hexane).

LRMS (ESI): (calc.) 423.46 (found) 424.16 (MH)+

Step 3: (Z)-methyl5-(dibenzo[b,f][1,4]oxazepin-11-yl)biphenyl-2-carboxylate 103

To a stirring solution of methyl5-(2-phenoxyphenylcarbamoyl)biphenyl-2-carboxylate 102 (0.723 g, 1.7mmol) in DCM (3 mL) was added PPA (40 g, 1.7 mmol). The reaction washeated to slowly distill off the DCM then stirred at 110° C. for 1 h.The reaction mixture was cooled to room temperature, poured into icewater then extracted with DCM. The combined organic layers were washedwith water, dried over Na₂SO₄, filtered and solvent evaporated toprovide 103 as a yellow solid (0.537 g, 78% yield) after purification byISCO (5 to 30% ethyl acetate in hexane).

LRMS (ESI): (calc.) 405.44 (found) 406.38 (MH)+

Step 4:(Z)-5-(dibenzo[b,f][1,4]oxazepin-11-yl)-N-hydroxybiphenyl-2-carboxamide104

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 103 to afford title compound(Z)-5-(dibenzo[b,f][1,4]oxazepin-11-yl)-N-hydroxybiphenyl-2-carboxamide104 (3% yield) as a white solid after purification by Gilson (55 to 95%MeOH in water).

¹H NMR (400 MHz, CD3OD) δ (ppm): 7.84 (d, J=1.6 Hz, 1H), 7.78 (d, J=8.0,2.0 Hz, 1H), 7.63-7.58 (m, 2H), 7.52-7.49 (m, 2H), 7.46-7.35 (m, 5H),7.30-7.20 (m, 5H). LRMS (ESI): (calc) 406.43 (found) 407.35 (MH)+

TABLE 7 Other compounds according to Scheme 15. Ex. Cpd # Structure NameCharacterization 15b 105

N2-hydroxy- N5-(2- phenoxyphenyl) biphenyl-2,5- dicarboxamide ¹H NMR(400 MHz, MeOH-d₄) δ (ppm): 7.87 (dd, J = 7.2, 2.4 Hz, 1H), 7.75 (dd, J= 8.0, 1.6 Hz, 1H), 7.64 (d, J = 1.6 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H),7.44-7.37 (m, 5H), 7.30-7.22 (m, 4H), 7.07 (dd, J = 1.8 Hz, 1H),7.02-6.99 (m, 1H), 6.96-6.94 (m, 2H) LRMS (ESI): (calc.) 424.45 (found)425.29 (MH)+

The following additional compounds were prepared according to theprocedures described herein and/or according to knowledge available toone of skill in the art.

TABLE 8 Cpd Structure Name Characterization 106

1-benzyl-N- hydroxy-3-phenyl- 1H-pyrazole-4- carboxamide ¹H NMR (400MHz, DMSO-d6) δ (ppm): 10.81 (s, 1H), 9.00 (s, 1H), 8.17 (s, 1H),7.79-7.74 (m, 2H), 7.44-7.32 (m, 8H), 5.41 (s, 2H) LRMS (ESI): (calc.)293.3 (found) 294.3 (MH)+ 107

1-(4- (benzyloxy) phenyl)-N- hydroxy-3- phenyl-1H- pyrazole-4-carboxamide ¹H NMR (400 MHz, DMSO-d6) δ (ppm): 10.87 (s, 1H), 9.10 (s,1H), 8.67 (s, 1H), 7.86-7.78 (m, 4H), 7.50-7.32 (m, 8H), 7.18 (d, J =9.2 Hz, 2H), 5.17 (s, 2H). LRMS (ESI): (calc.) 385.4 (found) 386.4 (MH)+108

3-(4- fluorophenyl)- N-hydroxy-1- phenyl-1H- pyrazole-4- carboxamide ¹HNMR (400 MHz, DMSO-d6) δ (ppm): 10.97 (br s, 1H), 9.18 (br s, 1H), 8.84(s, 1H), 8.01-7.91 (m, 4H), 7.63-7.56 (m, 2H), 7.45- 7.40 (m, 1H),7.36-7.28 (m, 2H) LRMS (ESI): (calc.) 297.3 (found) 298.2 (MH)+ 109

N-hydroxy-2-(4- morpholinophenyl)-4- phenylthiazole- 5-carboxamide ¹HNMR (400 MHz, CD3OD) δ (ppm): 7.90 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.0Hz, 2H), 7.47-7.40 (m, 3H), 7.04 (d, J =8.8 Hz, 2H), 3.84 (t, J = 5.2Hz, 4H), 3.28 (t, J = 4.8 Hz, 4H) LRMS (ESI): (calc.) 381.1 (found)382.3 (MH)+ 110

2-(benzo[b]thiophen- 3-yl)-N- hydroxy-4- phenylthiazole- 5-carboxamide¹H NMR (400 MHz, CD3OD) δ (ppm): 8.81 (d, J = 8.0 Hz, 1H), 8.35 (s, 1H),7.99 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 6.8 Hz, 2H), 7.56-7.41 (m, 5H)LRMS (ESI): (calc.) 352.0 (found) 353.2 (MH)+ 111

N-hydroxy-3- phenyl-1- (pyridin-2-yl)- 1H-pyrazole-4- carboxamide ¹H NMR(400 MHz, DMSO-d6) δ (ppm): 11.09 (br s, 1H), 9.17 (s, 1H), 8.95 (s,1H), 8.62-8.56 (m, 1H), 8.13-8.04 (m, 2H), 7.94- 7.88 (m, 2H), 7.52-7.44(m, 4H) LRMS (ESI): (calc.) 280.3 (found) 281.1 (MH)+ 112

N-hydroxy-2,5- diphenyloxazole- 4-carboxamide ¹H NMR (400 MHz, DMSO-d6)δ (ppm): 11.24 (s, 1H), 9.23 (s, 1H), 8.28-8.25 (m, 2H), 8.15-8.13 (m,2H), 7.62-7.58 (m, 3H), 7.56-7.46 (m, 3H) LRMS (ESI): (calc) 280.28(found) 281.17 (MH)+ 113

N-hydroxy-2,5- diphenylthiazole-4- carboxamide ¹H NMR (400 MHz, DMSO-d6)δ (ppm): 11.24 (s, 1H), 9.22 (s, 1H), 8.05-8.03 (m, 2H), 7.63-7.61 (m,2H), 7.55-7.54 (m, 3H), 7.48-7.44 (m, 3H) LRMS (ESI): (calc) 296.34(found) 297.18 (MH)+ 114

N-hydroxy-4- phenyl-2-(2- phenylacetamido) thiazole-5- carboxamide ¹HNMR (400 MHz, CD3OD) δ (ppm): 7.80-7.75 (m, 2H), 7.46- 7.28 (m, 9H),3.84 (s, 2H) LRMS (ESI): (calc.) 353.4 (found) 354.3 (MH)+ 115

N-hydroxy-3- phenylbenzofuran-2- carboxamide ¹H NMR (400 MHz, DMSO-d6) δ(ppm): 11.45 (br s, 1H), 9.27 (br s, 1H), 7.70-7.35 (m, 9H) LRMS (ESI):(calc.) 253.3 (found) 254.1 (MH)+ 116

5-(4- dimethylamino- phenyl)-N- hydroxybiphenyl- 2-carboxamide ¹H NMR(400 MHz, CD3OD) δ (ppm): 7.74 (s, 0.38H), 6.83-6.54 (m, 10H), 6.04 (d,J = 9.0 Hz, 2H), 2.18 (s, 6H). LRMS (ESI): (calc.) 332.4 (found) 333.3(MH)+ 117

N-hydroxy-4- phenyl-2- (piperidin-1- yl)thiazole-5- carboxamide ¹H NMR(400 MHz, DMSO-d6) δ (ppm): 10.71 (br s, 1H), 9.13 (s, 1H), 7.72-7.67(m, 2H), 7.44- 7.36 (m, 3H), 3.54-3.47 (m, 4H), 1.69-1.60 (m, 6H) LRMS(ESI): (calc.) 303.4 (found) 304.2 (MH)+ 118

N²-hydroxy-N⁵- phenylbiphenyl- 2,5- dicarboxamide ¹H NMR (400 MHz,DMSO-d6) δ (ppm): 10.92 (s, 1H), 10.38 (s, 1H), 9.10 (s, 1H), 7.98-7.96(m, 2H), 7.78 (dd, J = 8.8, 1.2 Hz, 2H), 7.54-7.34 (m, 8H), 7.14-7.10(m, 1H) LRMS (ESI): (calc) 332.35 (found) 333.33 (MH)+ 119

N-hydroxy-2- phenylbenzofuran-3- carboxamide ¹H NMR (400 MHz, DMSO-d6) δ(ppm): 11.17 (s, 1H), 9.35 (s, 1H), 7.92-7.89 (m, 2H), 7.69 (d, J = 8.2Hz, 1H), 7.60-7.33 (m, 6H). LRMS (ESI): (calc.) 253.3 (found) 252.1 (M −H)− 120

N-hydroxy-4- phenyl-2- (pyridin-3- yl)thiazole-5- carboxamide ¹H NMR(400 MHz, DMSO-d6) δ (ppm): 11.38 (br s, 1H), 9.52 (s, 1H), 9.25 (d, J =2.2 Hz, 1H), 8.81-8.76 (m, 1H), 8.49-8.42 (m, 1H), 7.96-7.86 (m, 2H),7.66- 7.61 (m, 1H), 7.59-7.45 (m, 3H) LRMS (ESI): (calc.) 297.3 (found)298.1 (MH)+ 121

2-(3,4- dihydroquinolin- 1(2H)-yl)-N- hydroxy-4- phenylthiazole-5-carboxamide ¹H NMR (400 MHz, CD3OD) δ (ppm): 7.94-7.88 (m, 1H), 7.79-7.72 (m, 2H), 7.48-7.38 (m, 3H), 7.29-7.20 (m, 2H), 7.14-7.07 (m, 1H)4.01 (t, J = 6.1 Hz, 2H), 2.84 (t, J = 6.3 Hz, 2H), 2.10-2.02 (m, 2H)LRMS (ESI): (calc.) 351.4 (found) 352.3 (MH)+ 122

N-hydroxy-4- phenyl-2- (pyridin-4- yl)thiazole-5- carboxamide ¹H NMR(400 MHz, DMSO-d6) δ (ppm): 11.39 (br s, 1H), 9.56 (s, 1H), 8.89-8.76(m, 2H), 8.06- 7.98 (m, 2H), 7.94-7.85 (m, 2H), 7.58-7.45 (m, 3H) LRMS(ESI): (calc.) 297.3 (found) 298.2 (MH)+ 123

N⁵-(2- aminophenyl)- N²- hydroxybiphenyl- 2,5- dicarboxamide ¹H NMR (400MHz, DMSO-d6) δ (ppm): 10.91 (s, 1H), 9.84 (s, 1H), 9.08 (s, 1H),8.02-7.96 (m, 2H), 7.51-7.39 (m, 6H), 7.15 (d, J = 8.0 Hz, 1H), 6.98 (t,J = 7.2 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.60 (t, J = 7.6 Hz, 1H),4.94 (s, 2H) LRMS (ESI): (calc) 347.37 (found) 348.30 (MH)+ 124

5-(1H- benzo[d]imidazol- 2-yl)-N- hydroxybiphenyl- 2-carboxamide ¹H NMR(400 MHz, DMSO-d6) δ (ppm): 13.06 (s, 1H), 10.91 (s, 1H), 9.08 (s, 1H),8.22-8.20 (m, 2H), 7.68 (d, J = 7.6 Hz, 1H), 7.57- 7.39 (m, 7H),7.26-7.19 (m, 2H) LRMS (ESI): (calc) 329.35 (found) 330.34 (MH)+ 125

N-hydroxy-5- (phenoxymethyl)-3- phenylthiophene-2- carboxamide ¹H NMR(400 MHz, DMSO-d6) δ (ppm): 10.94 (s, 1H), 9.19 (s, 1H), 7.48-7.30 (m,8H), 7.06-7.04 (m, 2H), 6.99-6.95 (m, 1H), 5.33 (s, 2H) LRMS (ESI):(calc) 325.38 (found) 326.31 (MH)+ 126

N-hydroxy-3- phenyl-5- (phenylsulfonamido) benzo[b] thiophene-2-carboxamide ¹H NMR (400 MHz, DMSO-d6) δ (ppm): 10.83 (br s, 1H), 10.33(br s, 1H), 9.21 (s, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.69-7.44 (m, 8H),7.23- 7.21 (m, 4H). LRMS (ESI): (calc.) 424.5 (found) 425.4 (MH)+ 127

N-hydroxy-1- phenyl-5- (trifluoromethyl)- 1H-pyrazole- 4-carboxamide ¹HNMR (400 MHz, CD3OD) δ (ppm): 7.92 (s, 1H), 7.58-7.55 (m, 3H), 7.48-7.46(m, 2H) LRMS (ESI): (calc.) 271.2 (found) 270.1 (MH)− 128

3-chloro-N- hydroxy-5- phenylthiophene-2- carboxamide ¹H NMR (400 MHz,DMSO-d6 ) δ (ppm): 11.01 (s, 1H), 9.35 (s, 1H), 7.74-7.71 (m, 2H), 7.62(s, 1H), 7.49-7.39 (m, 3H) LRMS (ESI): (calc) 253.70 (found) 254.08(MH)+ 129

N²-hydroxy-N⁵-(2- phenoxyphenyl) biphenyl-2,5- dicarboxamide ¹H NMR (400MHz, CD3OD) δ (ppm): 7.87 (dd, J = 7.2, 2.4 Hz, 1H), 7.75 (dd, J = 8.0,1.6 Hz, 1H), 7.64 (d, J = 1.6 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H),7.44-7.37 (m, 5H), 7.30-7.22 (m, 4H), 7.07 (dd, J = 1.8 Hz, 1H),7.02-6.99 (m, 1H), 6.96-6.94 (m, 2H) LRMS (ESI): (calc) 424.45 (found)425.29 (MH)+ 130

5-benzyl-N- hydroxy-3- phenylthiophene-2- carboxamide ¹H NMR (400 MHz,DMSO-d6) δ (ppm): 10.78 (s, 1H), 9.09 (s, 1H), 7.44-7.30 (m, 9H),7.27-7.22 (m, 1H), 7.08 (s, 1H), 4.16 (s, 2H) LRMS (ESI): (calc) 309.38(found) 310.26 (MH)+ 131

benzyl 2- (hydroxycarbamoyl)-3- phenylbenzo[b] thiophen-5- ylcarbamate¹H NMR (400 MHz, DMSO-d6) δ (ppm): 10.83 (br s, 1H), 9.90 (br s, 1H),9.20 (br s, 1H), 7.98-7.89 (m, 2H), 7.54-7.30 (m, 1H), 5.12 (s, 2H).LRMS (ESI): (calc.) 418.5 (found) 419.3 (MH)+ 132

2-(1- benzylpiperidin- 4-yl)-N- hydroxy-4- phenylthiazole- 5-carboxamide¹H NMR (400 MHz, CD3OD) δ (ppm): 7.80-7.76 (m, 2H), 7.49- 7.26 (m, 8H),3.54 (s, 2H), 3.13- 3.03 (m, 1H), 2.96-2.89 (m, 2H), 2.20-2.05 (m, 4H),1.84-1.72 (m, 2H) LRMS (ESI): (calc.) 393.5 (found) 394.4 (MH)+ 133

2-(1- benzoylpiperidin- 4-yl)-N- hydroxy-4- phenylthiazole-5-carboxamide (¹H NMR (400 MHz, CD3OD) δ (ppm): 7.81-7.75 (m, 2H), 7.54-7.41 (m, 8H), 4.81-4.70 (m, 1H), 3.96-3.82 (m, 1H), 3.50-3.40 (m, 3H),2.38-2.27 (m, 1H), 2.20- 2.10 (m, 1H), 2.00-1.80 (m, 2H) LRMS (ESI):(calc.) 407.5 (found) 408.3 (MH)+ 134

N-hydroxy-4′- methoxybiphenyl-2- carboxamide (DMSO-d6) d(ppm) 1H: 10.73(s, 1H), 8.96 (s, 1H), 7.50-7.46 (m, 1H), 7.38-7.32 (m, 3H), 7.34 (d, J= 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.78 (s, 3H). LRMS (ESI):(calc.) 243.26 (found) 244.2 (MH)+ 135

2-(6- fluoropyridin-3- yl)-N- hydroxybenzamide (DMSO) δ ppm) 1H: 10.85(s, 1H), 9.05 (s, 1H), 8.21 (d, 1H), 7.96 (t, 1H), 7.55 (m, 1H), 7.43(m, 3H), 7.24 (dd, 1H). LRMS (ESI): (calc.) 232.21 (found) 233.1 (MH)+136

N-hydroxy-2- (pyridin-3- yl)benzamide (DMSO-d6) δ ppm) 1H: 10.88 (s,1H), 9.04 (d, J = 1.2 Hz, 1H), 8.57 (dd, J = 0.8, 2.3 Hz, 1H), 8.54 (dd,J = 1.7, 4.9 Hz, 1H), 7.77 (dt, J = 2.3, 7.6 Hz, 1H), 7.55 (dd, J = 1.7,7.6 Hz, 1H), 7.47-7.42 (m, 4H) LRMS (ESI): (calc.) 214.22 (found) 215.1(MH)+ 137

3′-amino-N- hydroxybiphenyl- 2-carboxamide (DMSO-d6 ) δ ppm) 1H: 10.66(s, 1H), 8.91 (s, 1H), 7.45 (dd, J = 1.9, 7.6 Hz, 1H), 7.37-7.29 (m,3H), 6.99 (t, J = 7.6 Hz, 1H), 6.59 (t, J = 1.9 Hz, 1H), 6.54-6.50 (m,2H), 5.07 (bs, 2H) LRMS (ESI): (calc.) 228.25 (found) 229.1 (MH)+ 138

2-benzamido-N- hydroxy-4- phenylthiazole- 5-carboxamide (DMSO-d6) d(ppm)1H: 13.03 (br s, 1H), 8.21-8.16 (m, 1H), 8.02-7.96 (m, 2H), 7.83-7.76(m, 1H), 7.74- 7.40 (m, 6H) LRMS (ESI): (calc.) 339.4 (found) 340.3(MH)+ 139

2-(2,3- dihydrobenzofuran- 5-yl)-N- hydroxy-4- phenylthiazole-5-carboxamide (DMSO-d6) d(ppm) 1H: 11.20 (s, 1H), 9.37 (s, 1H),7.89-7.74 (m, 4H), 7.46-7.37 (m, 3H), 6.89 (d, J = 8.4 Hz, 1H), 4.61 (t,J = 8.8 Hz, 2H), 3.26 (t, J = 8.8 Hz, 2H). LRMS (ESI): (calc.) 338.4(found) 339.3 (MH)+ 140

N-hydroxy-4- phenyl-2- (thiophen-2- yl)thiazole-5- carboxamide (DMSO-d6)d(ppm) 1H: 11.30 (br s, 1H), 9.47 (s, 1H), 7.90-7.77 (m, 4H) , 7.56-7.44(m, 3H), 7.29- 7.24 (m, 1H) LRMS (ESI): (calc.) 302.4 (found) 303.1(MH)+ 141

N-hydroxy-2,4- diphenylpyrimidine-5- carboxamide (DMSO-d6) d(ppm) 1H:11.26 (br s, 1H), 9.45 (s, 1H), 8.93 (s, 1H), 8.57-8.51 (m, 2H),8.01-7.95 (m, 2H), 7.65-7.56 (m, 6H) LRMS (ESI): (calc.) 291.3 (found)292.2 (MH)+ 142

N-hydroxy-2-(4- methoxyphenyl)-4- phenylthiazole- 5-carboxamide(DMSO-d6) d(ppm) 1H: 11.21 (s, 1H), 9.38 (s, 1H), 7.94 (d, J = 8.8 Hz,2H), 7.81 (d, J = 7.3 Hz, 2H), 7.47-7.37 (m, 3H), 7.08 (d, J = 8.8 Hz,2H), 3.83 (s, 3H). LRMS (ESI): (calc.) 326.4 (found) 327.3 (MH)+ 143

4-(3- fluorophenyl)- N-hydroxy-2- phenylpyrimidine-5- carboxamide(DMSO-d6) d(ppm) 1H: 11.29 (br s, 1H), 9.51 (s, 1H), 8.98 (s, 1H),8.58-8.50 (m, 2H), 7.81-7.72 (m, 2H), 7.68-7.59 (m, 4H), 7.51- 7.44 (m,1H) LRMS (ESI): (calc.) 309.3 (found) 310.3 (MH)+ 144

N-hydroxy-4- phenyl-2-(1- (pyridin-4- ylmethyl)piperidin-4-yl)thiazole-5- carboxamide (DMSO-d6) δ ppm) 1H: 8.55 (dd, J = 4.5, 1.6Hz, 2H), 7.82-7.75 (m, 2H), 7.50-7.37 (m, 5H), 3.59 (s, 2H), 3.15-3.05(m, 1H), 2.95- 2.88 (m, 2H), 2.24-2.06 (m, 4H), 1.87-1.76 (m, 2H) LRMS(ESI): (calc.) 394.5 (found) 395.4 (MH)+ 145

N-hydroxy-4- phenyl-2-(1- (pyrrolidine-1- carbonyl)piperidin-4-yl)thiazole-5- carboxamide (MeOD-d4) δ ppm) 1H: 7.80-7.74 (m, 2H),7.49-7.40 (m, 3H), 3.95- 3.88 (m, 2H), 3.46-3.40 (m, 4H), 3.35-3.28 (m,1H), 3.05-2.92 (m, 2H), 2.22-2.15 (m, 2H), 1.94- 1.80 (m, 6H) LRMS(ESI): (calc.) 400.5 (found) 401.4 (MH)+ 146

N-hydroxy-2- (4-(2- morpholinoethoxy) phenyl)-4- phenylthiazole-5-carboxamide (DMSO-d6) δ ppm) 1H: 11.23 (br s, 1H), 9.40 (br s, 1H),7.94 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 7.0 Hz, 2H), 7.49-7.39 (m, 3H),7.10 (d, J = 9.0 Hz, 2H), 4.17 (t, J = 5.7 Hz, 2H), 3.58 (t, J = 5.7 Hz,4H), 2.72 (t, J = 5.6 Hz, 2H), 2.49-2.48 (m, 4H). LRMS (ESI): (calc.)425.5 (found) 426.4 (MH)+ 147

ethyl 4-(5- (hydroxycarbamoyl)-4- phenylthiazol-2- yl)piperidine-1-carboxylate (DMSO-d6) δ ppm) 1H: 7.86-7.79 (m, 2H), 7.48-7.37 (m, 3H),4.14- 4.04 (m, 4H), 3.36-3.24 (m, 1H), 3.10-2.90 (m, 2H), 2.15-2.06 (m,2H), 1.70-1.58 (m, 2H), 1.23 (t, J = 7.0 Hz, 3H) LRMS (ESI): (calc.)375.4 (found) 376.4 (MH)+ 148

N-hydroxy-2-(1- (methylsulfonyl) piperidin-4-yl)-4- phenylthiazole-5-carboxamide (MeOD-d4) δ ppm) 1H: 7.80-7.75 (m, 2H), 7.50-7.40 (m, 3H),3.90- 3.82 (m, 2H), 3.32-3.22 (m, 1H), 3.04-2.94 (m, 2H), 2.90 (s, 3H),2.35-2.25 (m, 2H), 2.03-1.90 (m, 2H) LRMS (ESI): (calc.) 381.5 (found)382.1 (MH)+ 149

N-hydroxy-2- phenyl-4- (pyridin-4- yl)pyrimidine- 5-carboxamide(DMSO-d6) δ ppm) 1H: 11.33 (br s, 1H), 9.52 (s, 1H), 9.05 (s, 1H), 8.82(dd, J = 4.5, 1.8 Hz, 2H), 8.56- 8.51 (m, 2H), 7.87 (dd, J = 4.3, 1.6Hz, 2H), 7.68-7.60 (m, 3H) LRMS (ESI): (calc.) 292.3 (found) 293.1 (MH)+150

2-benzhydryl- N-hydroxy-4- phenylthiazole- 5-carboxamide (DMSO-d6)d(ppm) 1H: 11.19 (s, 1H), 9.38 (s, 1H), 7.79-7.74 (m, 3H), 7.59-7.51 (m,2H), 7.49- 7.30 (m, 10H), 6.09 (s, 1H) LRMS (ESI): (calc.) 386.5 (found)387.3 (MH)+ 151

N-hydroxy-4- phenyl-2-(1- (phenylsulfonyl) piperidin-4- yl)thiazole-5-carboxamide (DMSO-d6) d(ppm) 1H: 7.85-7.67 (m, 7H), 7.47-7.37 (m, 3H),3.79- 3.71 (m, 2H), 3.19-3.10 (m, 1H), 2.55-2.50 (m, 2H), 2.21-2.12 (m,2H), 1.84-1.69 (m, 2H) LRMS (ESI): (calc.) 443.5 (found) 444.3 (MH)+ 152

2-(1-(2-(1H- indol-3- yl)ethyl)piperidin- 4-yl)-N- hydroxy-4-phenylthiazole- 5-carboxamide (MeOD-d4) d(ppm) 1H: 7.81-7.75 (m, 2H),7.63-7.59 (m, 1H), 7.49- 7.36 (m, 4H), 7.17-7.11 (m, 2H), 7.08-7.03 (m,1H), 3.50-3.42 (m, 2H), 3.35-3.30 (m, 1H), 3.19- 3.02 (m, 4H), 2.80-2.67(m, 2H), 2.38-2.29 (m, 2H), 2.17-2.03 (m, 2H) LRMS (ESI): (calc.) 446.6(found) 447.3 (MH)+ 153

N-hydroxy-4- phenyl-2- (pyridin-2- yl)thiazole-5- carboxamide (MeOD-d4)d(ppm) 1H: 8.63 (d, J = 4.3 Hz, 1H), 8.31 (d, J = 7.8 Hz, 1H), 8.02-7.95(m, 1H), 7.93-7.86 (m, 2H), 7.55-7.42 (m, 4H) LRMS (ESI): (calc.) 297.3(found) 298.1 (MH)+ 154

N-hydroxy-5-(4- methoxyphenyl- sulfonamido)-3- phenylbenzo[b]thiophene-2- carboxamide (DMSOD6) δ ppm) 1H: 10.78 (br s, 1H), 10.15 (brs, 1H), 9.19 (s, 1H), 7.91 (d, J = 9.2 Hz, 1H), 7.58 (d, J = 9.0 Hz,2H), 7.52-7.42 (m, 3H), 7.24-7.19 (m, 4H), 7.03 (d, J = 8.8 Hz, 2H) LRMS(ESI): (calc.) 454.5 (found) 455.2 (MH)+ 155

N-hydroxy-5- (2-(4- (trifluoromethyl) phenyl)acetamido) biphenyl-2-carboxamide (DMSO-d6) d(ppm) 1H: 10.71 (d, J = 1.6 Hz, 1H), 10.45 (s,1H), 8.93 (d, J =1.6 Hz, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 2.0Hz, 1H), 7.59 (dd, J = 8.4, 2.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H),7.42-7.32 (m, 6H), 3.80 (s, 2H) LRMS (ESI): (calc) 414.38 (found) 415.2(MH)+ 156

N-hydroxy-2,5- diphenyl-1H- pyrrole-3- carboxamide (DMSO-d6) d(ppm) 1H:11.56 (s, 1H), 10.56 (s, 1H), 8.75 (d, J = 1.6 Hz, 1H), 7.74-7.72 (m,2H), 7.68-7.65 (m, 2H), 7.42-7.37 (m, 4H), 7.33-7.29 (m, 1H), 7.24-7.20(m, 1H), 6.79 (d, J = 2.8 Hz, 1H) LRMS (ESI): (calc) 278.11 (found)279.2 (MH)+ 157

N-hydroxy-3- phenyl-5- (phenylmethyl- sulfonamido) benzo[b]thiophene-2-carboxamide (DMSO-d6) δ ppm) 1H: 10.86 (br s, 1H), 9.89 (br s, 1H),9.21 (s, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.54- 7.42 (m, 6H), 7.34-7.18(m, 6H), 4.39 (s, 2H). LRMS (ESI): (calc.) 438.5 (found) 439.2 (MH)+ 158

2-(1-(4- acetamidophenyl- sulfonyl)piperidin- 4-yl)-N- hydroxy-4-phenylthiazole- 5-carboxamide (DMSO-d6) δ ppm) 1H: 11.19 (br s, 1H),10.45 (s, 1H), 9.36 (br s, 1H), 7.91-7.85 (m, 2H), 7.79-7.70 (m, 4H),7.49-7.38 (m, 3H), 3.74- 3.67 (m, 2H), 3.20-3.09 (m, 1H), 2.54-2.46 (m,2H), 2.21-2.13 (m, 5H), 1.84-1.72 (m, 2H) LRMS (ESI): (calc.) 500.6(found) 501.5 (MH)+  158a

5-(3,4- dimethoxyphenyl- sulfonamido)-N- hydroxybiphenyl- 2-carboxamide(DMSO-d6) d(ppm) 1H: 10.68 (d, J = 1.8 Hz, 1H), 10.46 (s, 1H), 8.92 (d,J = 2.0 Hz, 1H), 7.41-7.24 (m, 8H), 7.14-7.09 (m, 3H), 3.80 (s, 3H),3.75 (s, 3H) LRMS (ESI): (calc) 428.10 (found) 429.45 (MH)+ 159

5-(benzylamino)- N-hydroxybiphenyl- 2-carboxamide (DMSO-d6) d(ppm) 1H:10.46 (S, 1H), 8.71 (s, 1H), 7.36-7.21 (m, 10H), 7.09 (d, J =8.8 Hz,1H), 6.70 (t, J = 6.0 Hz, 1H), 6.53-6.51 (m, 2H), 4.33 (d, J = 6.4 Hz,2H) LRMS (ESI): (calc) 318.14 (found) 319.37 (MH)+ 160

N-hydroxy-3- phenyl-5- (thiophene-2- sulfonamido) benzo[b]thiophene-2-carboxamide (DMSO-d6) d(ppm) 1H: 10.81 (br s, 1H), 10.41 (br s, 1H),9.20 (s, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.89 (dd, J = 4.9 Hz, 1H),7.52-7.41 (m, 4H) 7.32-7.23 (m, 4H), 7.11 (dd, J = 4.9, 3.7 Hz, 1H).LRMS (ESI): (calc.) 430.5 (found) 431.4 (MH)+ 161

N-hydroxy-2- phenyl-4- (phenylthio) pyrimidine-5- carboxamide (DMSO-d6)d(ppm) 1H: 8.79 (s, 1H), 7.96 (d, J = 7.0 Hz, 2H), 7.69-7.56 (m, 5H),7.53-7.47 (m, 1H), 7.44-7.37 (m, 2H) LRMS (ESI): (calc.) 323.4 (found)324.2 (MH)+ 162

N-hydroxy-5-((11- oxodibenzo[b,f] [1,4]oxazepin- 10(11H)- yl)methyl)biphenyl-2- carboxamide (DMSO-d₆) δ ppm) 1H: 10.77 (s, 1H), 8.96 (s,1H), 7.76 (dd, J = 7.6, 1.6 Hz, 1H), 7.63-7.58 (m, 1H), 7.55-7.52 (m,1H), 7.41-7.28 (m, 11H), 7.24-7.17 (m, 2H), 5.46 (s, 2H) LRMS (ESI):(calc) 436.14 (found) 437.49 (MH)+ 163

2-(4-benzyl- piperidin-1-yl)-N- hydroxy-4- phenylpyrimidine-5-carboxamide (MeOD-d4) d(ppm) 1H: 8.37 (s, 1H), 7.79-7.74 (m, 2H), 7.50-7.43 (m, 3H), 7.33-7.27 (m, 2H), 7.24-7.18 (m, 3H), 4.91 (m, 2H),3.00-2.90 (m, 2H), 2.60 (d, J = 7.0 Hz, 2H), 1.99-1.84 (m, 1H), 1.82-1.72 (m, 2H), 1.30-1.18 (m, 2H) LRMS (ESI): (calc.) 388.5 (found) 389.4(MH)+ 164

N-hydroxy-1,4- diphenyl-1H- pyrrole-3- carboxamide (MeOD-d4) δ ppm) 1H:7.60-7.46 (m, 7H), 7.38 (d, J = 2.5 Hz, 1H), 7.36-7.29 (m, 3H), 7.22 (t,J = 7.3 Hz, 1H). LRMS (ESI): (calc.) 278.1 (found) 279.2 (MH)+

Example 16a, 16b, 16c, 16d

-   (5-(hydroxycarbamoyl)-4-phenylthiophen-2-yl)methyl benzylcarbamate    (180)-   (5-(hydroxycarbamoyl)-4-phenylthiophen-2-yl)methyl    benzyl(methyl)carbamate (181)-   5-((benzyl(methyl)amino)methyl)-N-hydroxy-3-phenylthiophene-2-carboxamide    (182)-   N2-hydroxy-N5,3-diphenylthiophene-2,5-dicarboxamide (183)

Step 1: 4-(tert-butyldimethylsilyloxy)-1-phenylbut-2-yn-1-one (167)

To a solution of tert-Butyldimethyl(2-propynyloxy)silane 166 (7.99 mL,39.4 mmol) in 80 mL of THF at −78° C. was added dropwise N-BUTYLLITHIUM(15.76 mL, 39.4 mmol). The resulting mixture was then warmed up slowlyto −30° C. and stirred for 30 min. A solution ofN-Methoxy-N-methylbenzamide 165 (5 mL, 32.8 mmol) in 5 mL of THF wasadded dropwise and the solution was warmed slowly to room temperatureand stirred 2 hours. Aqueous 5% HCl was added to quench the reaction andthe product was extracted twice with ethyl acetate. The combined organiclayers were washed with a saturated solution of bicarbonate and brine,dried over sodium sulfate and filtered. The solvents were removed invacuo and the crude material was purified by ISCO (120 g column, 0-30%ethyl acetate in hexanes) to yield 99% of a yellow oil 167 (8.924 g)

LRMS (ESI):(calc) 274.14 (found) 275.05 (MH)+

Step 2: methyl5-((tert-butyldimethylsilyloxy)methyl)-3-phenylthiophene-2-carboxylate(168)

To a solution of 167 (8.924 g, 32.5 mmol) in THF was added methylthioglycolate (4.36 mL, 48.8 mmol) and stirred 2 hours at roomtemperature. MAGNESIUM SULFATE (3.91 g, 32.5 mmol) was added and thereaction mixture was stirred for 1 hour. Then CESIUM CARBONATE (10.60 g,32.5 mmol) in 30 mL of MeOH was added and stirred for an additional 2hours at room temperature. The reaction mixture was filtered and thefiltrate was concentrated in vacuo. The residue was dissolved in ethylacetate and washed with brine, dried over sodium sulfate and filtered.The solvent was evaporated and the residue was purified by silica gelchromatography (0%-5% ethyl acetate in hexanes) to yield 168 in 54%(6.389 g) as an orange solid

LRMS (ES): (calc) 362.14 (found) 363.38 (MH)+

Step 3: methyl 5-(hydroxymethyl)-3-phenylthiophene-2-carboxylate (169)

To a solution of 168 (6.389 g, 17.62 mmol) in 93 mL of MeOH was addedconcentrated HCl (7 ml, 85 mmol) and stirred at room temperature for 45min. The reaction mixture was concentrated under vacuum; the oil wasdissolved in ethyl acetate, washed with a saturated solution of sodiumbicarbonate, water, brine, dried with sodium sulfate, filtered andconcentrated under vacuum. The residue was purified by ISCO (10%-50%ethyl acetate in hexanes) to yield 169 in 99% (4.35 g) as light brownoil

LRMS (ESI): (calc) 248.05 (found) 249.14 (MH)+

Step 4: methyl5-((benzylcarbamoyloxy)methyl)-3-phenylthiophene-2-carboxylate (170)

To a solution of 169 (0.900 g, 3.62 mmol) in THF was added1,1′-carbonyldiimidazole (0.588 g, 3.62 mmol) and stirred at roomtemperature for 90 min. Then BnNH₂ (0.396 mL, 3.62 mmol), TEA (0.505 mL,3.62 mmol) and 1,8-Diazabicyclo[5.4.0]undec-7-ene (0.546 mL, 3.62 mmol)were added and stirred at room temperature for an additional 2 hours.The reaction mixture was diluted with ethyl acetate, washed with water,brine, dried over sodium sulfate, filtered and concentrated undervacuum. The residue was purified by ISCO (40 g column, 0-45% ethylacetate in hexanes) to yield in 82% (1.13 g) compound 170 as a pinksolid.

Step 5: methyl5-((benzyl(methyl)carbamoyloxy)methyl)-3-phenylthiophene-2-carboxylate(171)

To a solution of 170 (0.620 g, 1.625 mmol) in 10 mL of THF was added NaH(0.098 g, 2.438 mmol) and stirred at room temperature for 20 min. ThenMeI (0.5 ml, 8.00 mmol) was added and stirred for an additional 2 hoursat 50° C. The reaction mixture was cooled down at room temperature,quenched with 2 mL of MeOH, diluted with ethyl acetate, washed withbrine, dried over sodium sulfate, filtered and concentrated undervacuum. The residue was purified by ISCO (40 g column, 5%-30% ethylacetate in hexanes) to yield in 53% (342 mg) compound 171 as colorlessoil.

LRMS (ESI):(calc) 395.12 (found) 396.40 (MH)+

Step 6: (5-(hydroxycarbamoyl)-4-phenylthiophen-2-yl)methylbenzylcarbamate (180)

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 170 to afford title compound 180 (46% yield,110 mg) as a white solid after purification by Gilson (45%-95% MeOH inwater).

LRMS (ESI):(calc) 382.10 (found) 383.11 (MH)+

(5-(hydroxycarbamoyl)-4-phenylthiophen-2-yl)methylbenzyl(methyl)carbamate (181)

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 171 to afford title compound 181 (37% yield,127 mg) as colorless foam after purification by Gilson (50%-95% MeOH inwater).

LRMS (ESI):(calc) 396.11 (found) 397.33 (MH)+

Step 7: methyl 5-formyl-3-phenylthiophene-2-carboxylate (172)

DMSO (0.643 ml, 9.06 mmol) in 4 mL of DCM at −70° C. was added dropwiseto a solution of oxalyl chloride (0.529 ml, 6.04 mmol) in 10 mL of DCMat −78° C. and stirred for 10 min. Then 169 (0.75 g, 3.02 mmol) in 4 mLof DCM and TEA in 4 mL DCM were added dropwise, stirred for anadditional 10 min and warmed up slowly to 0° C. The reaction mixture waspoured into an ice-cooled solution of NaHCO₃ (ss) and extract theproduct with DCM, washed with brine, dried over sodium sulfate,filtered, concentrated under vacuum to yield compound 172 (706 mg, 95%)as a beige solid.

LRMS (ESI):(calc) 246.04 (found) 247.16 (MH)+

Step 8: methyl5-((benzyl(methyl)amino)methyl)-3-phenylthiophene-2-carboxylate (173)

To a solution of 172 (0.706 g, 2.87 mmol) in DCE (15 mL) was addedN-Methylbenzylamine (0.388 mL, 3.01 mmol) and sodiumtriacetoxyborohydride (0.851 g, 4.01 mmol) and stirred for 18 hours. Thereaction mixture was diluted in DCM and washed with a saturated solutionof sodium bicarbonate. The organic layer was dried over sodium sulfate,filtered and evaporated. The crude residue was purified by ISCO (40 gcolumn, 0-30% ethyl acetate in hexanes) to yield compound 173 (951 mg,94%) a colorless oil.

LRMS (ESI):(calc) 351.13 (found) 352.33 (MH)+

Step 9:5-((benzyl(methyl)amino)methyl)-N-hydroxy-3-phenylthiophene-2-carboxamide(182)

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 173 to afford title compound 182 (61% yield,580 mg) as colorless foam after purification by ISCO (30%-60% Ethylacetate in hexanes).

LRMS (ESI): (calc) 352.12 (found) 353.39 (MH)+

Step 10: 5-(methoxycarbonyl)-4-phenylthiophene-2-carboxylic acid (174)

To a solution of 169 (1.20 g, 4.83 mmol) in 30 mL of acetone was addeddropwise Jones reagent (5 mL, 1.3M, 6.5 mmol) and stirred at roomtemperature for 1 hour. The reaction mixture was quenched with 10 mL ofIPA, stirred for 10 min, filtered over a pad of Celite®. The filtratewas concentrated under vacuum, diluted in ether, washed with brine,dried over sodium sulfate, filtered, concentrated under vacuum to yieldcompound 174 (1.156 g, 91%) as yellow solid.

LRMS (ESI): (calc) 262.03 (found) 261.16 (M−1)

Step 11: methyl 3-phenyl-5-(phenylcarbamoyl)thiophene-2-carboxylate(175)

To a solution of 174 (0.334 g, 1.273 mmol) in 6 mL DMF was added PhNH₂(0.128 ml, 1.401 mmol), followed by BOP (0.620 g, 1.401 mmol) and TEA(0.355 ml, 2.55 mmol). The mixture was stirred for 1 h at roomtemperature and then poured into water. The product was extracted withethyl acetate twice and the combined organic phases were washed withwater and brine. The solution was dried over sodium sulfate, filteredand evaporated in vacuo. The crude residue was purified by ISCO (24 gcolumn, 0%-100% ethyl acetate in hexanes) to yield compound 175 (285 mg,66%) a off-white solid.

LRMS (ESI): (calc) 337.08 (found) 338.33 (MH)+

Step 12: N2-hydroxy-N5,3-diphenylthiophene-2,5-dicarboxamide (183)

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound 175 to afford title compound 183 (64% yield,182 mg) as a white solid after purification by Gilson (55%-95% MeOH inwater).

LRMS (ESI): (calc) 338.07 (found) 339.31 (MH)+

TABLE 8 Compounds according to Scheme 16 and Scheme 15 Ex. Cpd #Structure Name Characterization 16 180

(5-(hydroxy- carbamoyl)-4- phenylthiophen-2- yl)methyl benzylcarbamate(DMSO-d₆) δ ppm) 1H: 10.91 (s, 1H), 9.18 (s, 1H), 7.91 (t, J =6.3 Hz,1H), 7.46-7.22 (m, 11H), 5.22 (s, 2H), 4.21 (d, J = 6.1 Hz, 2H) LRMS(ESI): (calc) 382.10 (found) 383.11 (MH)+ 181

(5-(hydroxy- carbamoyl)-4- phenylthiophen-2- yl)methyl benzyl(methyl)carbamate (MeOD-d4) δ ppm) 1H: 7.49-7.18 (m, 11H), 3.53 (d, J = 3.6 Hz,2H), 4.50 (s, 2H), 2.89, 2.87 (2S, CH3, rotamers) LRMS (ESI): (calc)396.11 (found) 397.33 (MH)+ 182

5-((benzyl(methyl) amino)methyl)-N- hydroxy-3- phenylthiophene-2-carboxamide (DMSO-d6) δ ppm) 1H: 10.85 (s, 1H), 9.13 (s, 1H), 7.47-7.45(m, 2H), 7.41-7.24 (m, 8H), 7.14 (s, 1H), 3.74 (s, 2H), 3.57 (s, 2H),2.19 (s, 3H) LRMS (ESI): (calc) 352.12 (found) 353.39 183

N2-hydroxy- N5,3- diphenyl- thiophene-2,5- dicarboxamide (DMSO-d6) δppm) 1H: 11.15 (s, 1H), 10.35 (s, 1H), 9.33 (s, 1H), 8.21 (s, 1H),7.75-7.72 (m, 2H), 7.55-7.53 (m, 2H), 7.48- 7.45 (m, 2H), 7.42-7.36 (m,3H), 7.15-7.11 (m, 1H) LRMS (ESI): (calc) 338.07 (found) 339.31 (MH)+184

(E)-5- (dibenzo[b,f] [1,4]oxazepin- 11-yl)-N- hydroxy-3-phenylthiophene-2- carboxamide (DMSO-d6) δ ppm) 1H: 11.18 (s, 1H), 9.34(s, 1H), 7.73-7.67 (m, 2H), 7.54-7.52 (m, 2H), 7.45- 7.25 (m, 10H) LRMS(ESI): (calc) 412.09 (found) 413.30 (MH)+

Example 17a-g Compounds 201-207 Step 1: (Z)-methyl4-(3-bromophenyl)-4-hydroxy-2-oxobut-3-enoate II

In a 100 mL round-bottomed flask was dissolved 3′-bromoacetophenone (I)(10.03 mL, 75 mmol) and dimethyl oxalate (8.90 g, 75 mmol) in DMF (25mL) to give a pale orange suspension. Sodium hydride (3.62 g, 90 mmol)was added at 0° C. in portions, over 1 h (CAUTION! Vigorous bubbling!).The mixture was stirred at room temperature overnight, diluted withethyl acetate, washed twice with water, then brine, then dried withNaSO₄, and the solvent evaporated in vacuo. The residue was treated withaqueous 3M HCl to obtain a brown suspension, which was trituratedovernight and filtered to obtain product II as a yellow solid (18.4 g,64.5 mmol, 86%).

Step 2: Preparation of III-VII

In a 15 ml pressure vessel, II (1 g, 3.51 mmol) and a functionalizedhydrazine (HCl salt, 3.51 mmol) were dissolved in methanol (25 mL).(Four drops concentrated aqueous HCl was added if the hydrazine was usedas its free base.) The flask was heated at 100° C. for 16 h. Aftercooling, the solvent was evaporated to yield the desired product.

Methyl 1-benzyl-5-(3-bromophenyl)-1H-pyrazole-3-carboxylate III

Using II (4.08 g, 14.3 mmol) and benzylhydrazide dihydrochloride (2.79g, 14.3 mmol). 1.7 g (4.58 mmol, 32%) of III isolated as a thick yellowoil.

Methyl 5-(3-bromophenyl)-1-tert-butyl-1H-pyrazole-3-carboxylate IV

Using II (1 g, 3.51 mmol) and tert-butylhydrazine hydrochloride (0.437g, 3.51 mmol). Purified by silica gel chromatography (0-25% EtOAc/Hex,40 g silica column) get 742 mg (2.2 mmol, 63%) of IV as a yellow solid.

Methyl 5-(3-bromophenyl)-1-phenyl-1H-pyrazole-3-carboxylate V

Using II (1 g, 3.51 mmol) and phenylhydrazine (0.348 mL, 3.51 mmol).Purified by silica gel chromatography (0-20% EtOAc/Hex, 40 g silicacolumn) to get 816 mg (2.2 mmol, 63%) of V as a yellow foam.

Methyl5-(3-bromophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylate VI

Using II (1 g, 3.51 mmol) and 2,4-dichlorophenylhydrazine hydrochloride(0.749 g, 3.51 mmol). Crude material was triturated in ether to obtain920 mg (2.16 mmol, 62%) of VI as a light yellow powder.

Methyl5-(3-bromophenyl)-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-3-carboxylateVII

Using II (1 g, 3.51 mmol) and 3-(trifluoromethyl)phenylhydrazine (0.512mL, 3.51 mmol). Crude material was triturated in hexanes to obtain 1.19g (2.8 mmol, 80%) of VII as a light yellow powder.

Step 3: Preparation of XI-XV

The aryl bromide III-VII and bis(tri-t-butylphosphine)palladium(0)(0.044 equiv) were dissolved in Toluene (5 ml) in a 15 mL pressureflask, under a nitrogen atmosphere, to give an orange solution. An amine(1.3 equiv) and cesium carbonate (2.2 equiv) were then added and themixture left to stir at 110° C. overnight. After cooling the suspensionwas filtered through Celite®, washed the solid with ethyl acetate,concentrated the filtrate and the residue was purified via silica-gelchromatography column (0-50% EtOAc/Hex) to obtain the desired productXI-XV.

Methyl 1-benzyl-5-(3-morpholinophenyl)-1H-pyrazole-3-carboxylate XI

Using III (500 mg, 1.34 mmol) and morpholine gave 369 mg (0.98 mmol,73%) of XI as a yellow foam.

Methyl 5-(3-morpholinophenyl)-1-phenyl-1H-pyrazole-3-carboxylate XII

Using V (330 mg, 0.92 mmol) and morpholine gave 48 mg (0.13 mmol, 14%)of XII as a yellow foam.

Methyl1-(2,4-dichlorophenyl)-5-(3-morpholinophenyl)-1H-pyrazole-3-carboxylateXIII

Using VI (200 mg, 0.46 mmol) and morpholine gave 107 mg (0.24 mmol, 53%)of XIII as a colorless foam.

Methyl1-(2,4-dichlorophenyl)-5-(3-(indolin-1-yl)phenyl)-1H-pyrazole-3-carboxylateXIV

Using VI (200 mg, 0.46 mmol) and indoline gave 55 mg (0.12 mmol, 25%) ofXIV as a colorless foam.

Methyl5-(3-morpholinophenyl)-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-3-carboxylateXV

Using VII (250 mg, 0.58 mmol) and morpholine gave 123 mg (0.28 mmol,49%) of XV as a colorless foam.

Step 4: Preparation of IX, X and XVI-XX

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound III, IV, XI-XV to afford title compound IX, Xand XVI-XX as a white powder.

1-benzyl-5-(3-bromophenyl)-N-hydroxy-1H-pyrazole-3-carboxamide IX (cpd201) 200 mg of III yield 164 mg of IX as a white solid (0.44 mmol, 85%)5-(3-bromophenyl)-1-tert-butyl-N-hydroxy-1H-pyrazole-3-carboxamide X(cpd 202) 200 mg of IV yield 137 mg of X as a white solid (0.405 mmol,68%) 1-Benzyl-N-hydroxy-5-(3-morpholinophenyl)-1H-pyrazole-3-carboxamideXVI (cpd 203)

Using XI (100 mg, 0.26 mmol) yield 68 mg (0.18 mmol, 68%) of XVI as awhite powder.

N-Hydroxy-5-(3-morpholinophenyl)-1-phenyl-1H-pyrazole-3-carboxamide XVII(cpd 204)

Using XII (48 mg, 0.13 mmol) yield 40 mg (0.11 mmol, 83%) of XVII as awhite powder.

1-(2,4-Dichlorophenyl)-N-hydroxy-5-(3-morpholinophenyl)-1H-pyrazole-3-carboxamideXVIII (cpd 205)

Using XIII (107 mg, 0.24 mmol) yield 62 mg (0.143 mmol, 58%) of XVIII asa white powder.

1-(2,4-Dichlorophenyl)-N-hydroxy-5-(3-(indolin-1-yl)phenyl)-1H-pyrazole-3-carboxamideXIX (cpd 206)

Using XIV (55 mg, 0.12 mmol) yield 45 mg (0.09 mmol, 82%) of XIX as awhite powder.

N-Hydroxy-5-(3-morpholinophenyl)-1-(3-(trifluoromethyl)phenyl)-1H-pyrazole-3-carboxamideXX (cpd 207)

Using XV (123 mg, 0.28 mmol) yield 105 mg (0.24 mmol, 85%) of XX as awhite powder.

Example 185-(3′-(trifluoromethyl)biphenyl-4-yl)-1H-pyrazole-3-carboxamide (cpd200, XV) Step 1: methyl 5-(3-bromophenyl)-1H-pyrazole-3-carboxylate XXII

HCl in dioxane (4M, 3.56 mL, 14.23 mmol) was added to a solution of thecarboxylic acid XXI (950 mg, 3.56 mmol) in MeOH (15 mL) and the reactionstirred at room temperature for 16 h. The solvent was removed in vacuoand the residue diluted with ethyl acetate and washed once withsaturated sodium bicarbonate solution, twice with water, once withbrine, dried (MgSO₄) and removed solvent in vacuo to obtain XXII as anoff-white powder (810 mg, 2.88 mmol, 81%).

Step 2: methyl5-(3′-(trifluoromethyl)biphenyl-3-yl)-1H-pyrazole-3-carboxylate XXIII

In a 75 mL pressure flask, XXII (150 mg, 0.534 mmol), was dissolved inDME (5 mL) followed by addition of 3-trifluoromethylphenylboronic acid(111 mg, 0.587 mmol), and Pd(PPh₃)₄ (30.8 mg, 0.027 mmol) to give anorange solution. Sodium carbonate (2M solution, 0.320 mL, 0.640 mmol)was then added and refluxed overnight. The mixture was cooled to roomtemperature, filtered through silica and Celite®, washed the solids withethyl acetate and the solvent was removed in vacuo. The residue wassuspended in dichloromethane-ether, triturated and filtered to obtainXXIII as a white solid (98 mg, 0.283 mmol, 53%).

Step 3:N-hydroxy-5-(3′-(trifluoromethyl)biphenyl-3-yl)-1H-pyrazole-3-carboxamideXXIV

The procedure was followed as outlined in Scheme 5, Step 3 replacingcompound 49 with compound XXIII (98 mg, 0.283 mmol) to afford titlecompound XIV as a white solid (75 mg, 0.216 mmol, 76%).

Step 4: 5-(3′-(trifluoromethyl)biphenyl-3-yl)-1H-pyrazole-3-carboxamideXXV (cpd 200)

To a solution of XIV (50 mg, 0.144 mmol) in MeOH (10 ml) and water (1ml) was added ammonium chloride (15.40 mg, 0.288 mmol) and zinc powder(85 mg, 1.296 mmol) and the reaction mixture was heated to reflux for 4hours. The reaction mixture was cooled down and filtered the suspensionthrough Celite® and concentrated. The residue was purified via reversephase column chromatography (40-80% MeOH/H₂O) to obtain XXV (5.8 mg,0.018 mmol, 12%) as a white solid.

Table 9

The following additional compounds were prepared according to theprocedures described herein and/or according to knowledge available toone of skill in the art.

Cpd # Structure Name Characterization 200

5-(3′- (trifluoromethyl) biphenyl-4-yl)-1H- pyrazole-3- carboxamide(MeOD-d4) δ ppm) 1H: 7.66-7.95 (m, 8H), 7.13 (s, 1H). LRMS (ESI):(calc.) 331.09 (found) 332.37 (MH)+ 201

1-benzyl-5-(3- bromophenyl)-N- hydroxy-1H- pyrazole-3- carboxamide(MeOD-d4) d(ppm) 1H: 7.59 (m, 1H), 7.48 (s, 1H), 7.24-7.34 (m, 5H), 7.03(s, 1H), 7.02 (s, 1H), 6.83 (s, 1H), 5.41 (s, 2H). LRMS (ESI): (calc.)371.3 (found) 372.17 (MH)+ 202

5-(3-bromophenyl)- 1-tert-butyl-N- hydroxy-1H- pyrazole-3- carboxamide(MeOD-d4) d(ppm) 1H: 7.64 (m, 1H), 7.57 (s, 1H), 7.37 (m, 2H), 6.58 (s,1H), 1.48 (s, 9H). LRMS (ESI): (calc.) 337.04 (found) 336.2 (M)− 203

1-benzyl-N- hydroxy-5-(3- morpholinophenyl)- 1H-pyrazole-3- carboxamide(MeOD-d4) d(ppm) 1H: 7.29 (m, 4H), 7.03 (m, 3H), 6.75-6.85 (m, 3H), 5.41(s, 2H), 3.74 (m, 4H), 2.97 (m, 4H). LRMS (ESI): (calc.) 378.17 (found)379.36 (MH)+ 204

N-hydroxy-5-(3- morpholinophenyl)- 1-phenyl-1H- pyrazole-3- carboxamide(DMSO-d6) d(ppm) 1H: 11.1 (s, 1H), 9.0 (s, 1H), 7.43 (m, 3H), 7.32 (m,2H), 7.17 (t, J = 8 Hz, 1H), 6.98 (s, 1H), 6.93 (dd, J = 1.6 Hz, 8.4 Hz,1H), 6.79 (s, 1H,), 6.62 (d, J = 7.6 Hz, 1H), 3.66 (t, J = 4.8 Hz, 4H),2.97 (t, J = 4.8 Hz, 4H). LRMS (ESI): (calc.) 364.15 (found) 365.38(MH)+ 205

1-(2,4- dichlorophenyl)-N- hydroxy-5-(3- morpholinophenyl)-1H-pyrazole-3- carboxamide (MeOD-d4) d(ppm) 1H: 7.17-7.63 (m, 4H), 6.91-6.99 (m, 2H), 6.71-6.76 (m, 2H), 3.76 (t, J = 4.8 Hz, 4H), 2.97 (t, J =4.4 Hz, 4H). LRMS (ESI): (calc.) 432.08 (found) 431.13 (M)− 206

1-(2,4- dichlorophenyl)-N- hydroxy-5-(3- (indolin-1- yl)phenyl)-1H-pyrazole-3- carboxamide (MeOD-d4) d(ppm) 1H: 7.68 (m, 1H), 7.59 (m, 2H),7.33 (t, J = 8 Hz, 1H), 7.12 (d, J = 7.6 Hz, 2H), 6.96 (m, 4H), 6.71 (t,J = 7.6 Hz, 1H), 6.44 (d, J = 8 Hz, 1H), 3.78 (t, J = 8 Hz, 2H), 3.04(t, J = 8.4 Hz, 2H). LRMS (ESI): (calc.) 464.08 (found) 465.37 (MH)+ 207

N-hydroxy-5-(3- morpholinophenyl)- 1-(3- (trifluoromethyl)phenyl)-1H-pyrazole- 3-carboxamide (MeOD-d4) d(ppm) 1H: 7.69 (s, 2H),7.59 (m, 2H), 7.25 (t, J = 8 Hz, 1H), 6.99 (m, 2H), 6.77 (m, 2H), 3.75(t, J = 4.8 Hz, 4H), 2.99 (t, J = 4.8 Hz, 4H). LRMS (ESI): (calc.)432.14 (found) 431.35 (M)− 208

2-(2,4- diphenylthiazol-5- yl)-N- hydroxyacetamide (MeOD-d4) d(ppm) 1H:8.02-7.96 (m, 2H), 7.75- 7.71 (m, 2H), 7.56-7.44 (m, 6H), 3.79 (s, 2H)LRMS (ESI): (calc.) 310.4 (found) 311.2 (MH)+ 209

3-(1-(4- bromophenyl)-3- phenyl-1H-pyrazol- 4-yl)-N- hydroxypropanamide(DMSO-d6) d(ppm) 1H: 10.49 (br s, 1H), 8.79 (br s, 1H), 8.44 (s, 1H),7.90- 7.84 (m, 2H), 7.77-7.71 (m, 4H), 7.56-7.49 (m, 2H), 7.47-7.42 (m,1H), 2.93 (t, J = 7.4 Hz, 2H), 2.37 (t, J = 7.2 Hz, 2H) LRMS (ESI):(calc.) 386.2 (found) 386.3 (MH)+

Where possible, the compounds in this application were named usingChemdraw Ultra version 9 or 10, which is available throughCambridgesoft.co, 100 Cambridge Park Drive, Cambridge, Mass. 02140,

Meta- and para-substituted aryl or heteroaryl hydroxamates are very wellknown as HDAC inhibitors. Ortho-substitutions are detrimental for thepotency of HDAC inhibitors; however small groups substituents such ashalo can be tolerated.

We have unexpectedly found that o-substituted aryl or heteroarylhydroxamates having a much bigger but flat aromatic or heteroaromaticsubstituent such as phenyl or thienyl are not only well tolerated butcause an increase in HDAC inhibitory activity and impart selectivity forhistone deacetylase-4, -5, -6, -7, -8, -9 and/or -11.

Compositions

In a second aspect, the invention provides compositions comprising acompound according to the invention or an N-oxide, hydrate, solvate,pharmaceutically acceptable salt, complex or prodrug thereof, or aracemic or scalemic mixture, diastereomer, enantiomer or tautomerthereof, and a pharmaceutically acceptable carrier, excipient, ordiluent. Compounds of the invention may be formulated by any method wellknown in the art and may be prepared for administration by any route,including, without limitation, parenteral, oral, sublingual,transdermal, topical, intranasal, intratracheal, intravenous orintrarectal. In certain embodiments, compounds of the invention areadministered intravenously in a hospital setting. In certain otherembodiments, administration may be by the oral route. The compositionsmay be in the form of liquid solutions or suspensions; for oraladministration, formulations may be in the form of tablets or capsules;and for intranasal formulations, in the form of powders, nasal drops oraerosols. The compositions of the invention may be administeredsystemically or locally.

The characteristics of the carrier will depend on the route ofadministration. As used herein, the term “pharmaceutically acceptable”means a non-toxic material that is compatible with a biological systemsuch as a cell, cell culture, tissue, or organism, and that does notinterfere with the effectiveness of the biological activity of theactive ingredient(s). Thus, compositions according to the invention maycontain, in addition to the inhibitor, diluents, fillers, salts,buffers, stabilizers, solubilizers, and other materials well known inthe art. The preparation of pharmaceutically acceptable formulations isdescribed in, e.g., Remington's Pharmaceutical Sciences, 18th Edition,ed. A. Gennaro, Mack Publishing Co., Easton, Pa., 1990.

In one embodiment of the second aspect, the composition comprises acompound, N-oxide, hydrate, solvate, pharmaceutically acceptable salt,complex or prodrug of a compound according to the present invention asdescribed herein present in at least about 30% enantiomeric ordiastereomeric excess. In certain embodiments of the invention, thecompound, N-oxide, hydrates, solvate, pharmaceutically acceptable salt,complex or prodrug is present in at least about 50%, at least about 80%,or even at least about 90% enantiomeric or diastereomeric excess. Incertain other embodiments of the invention, the compound, N-oxide,hydrate, solvate, pharmaceutically acceptable salt, complex or prodrugis present in at least about 95%, alternatively at least about 98% andalternatively at least about 99% enantiomeric or diastereomeric excess.In other embodiments of the invention, a compound, N-oxide, hydrate,solvate, pharmaceutically acceptable salt, complex or prodrug is presentas a substantially racemic mixture. In certain embodiments, thecomposition further comprises an additional therapeutic or inhibitoryagent.

As used herein, the term “pharmaceutically acceptable salts” is intendedto mean salts that retain the desired biological activity of theabove-identified compounds and exhibit minimal or no undesiredtoxicological effects. Examples of such salts include, but are notlimited to acid addition salts formed with inorganic acids (for example,hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid,nitric acid, and the like), and salts formed with organic acids such asacetic acid, oxalic acid, tartaric acid, succinic acid, malic acid,ascorbic acid, benzoic acid, tannic acid, pamoic acid, alginic acid,polyglutamic acid, naphthalenesulfonic acid, naphthalenedisulfonic acid,and polygalacturonic acid. The compounds can also be administered aspharmaceutically acceptable quaternary salts known by those skilled inthe art, which specifically include the quaternary ammonium salt of theformula —NR+Z—, wherein R is hydrogen, alkyl, or benzyl, and Z is acounterion, including chloride, bromide, iodide, —O-alkyl,toluenesulfonate, methylsulfonate, sulfonate, phosphate, or carboxylate(such as benzoate, succinate, acetate, glycolate, maleate, malate,citrate, tartrate, ascorbate, benzoate, cinnamoate, mandeloate,benzyloate, and diphenylacetate). As used herein, the term “salt” isalso meant to encompass complexes, such as with an alkaline metal or analkaline earth metal.

The active compound is included in the pharmaceutically acceptablecarrier or diluent in an amount sufficient to deliver an inhibition ortherapeutic effective amount without causing undesirable toxic effects.In certain embodiments, a dose of the active compound for all of theabove-mentioned conditions is in the range from about 0.01 to 300 mg/kg,for example 0.1 to 100 mg/kg per day, alternatively 0.5 to about 25 mgper kilogram body weight of the recipient per day. A typical topicaldosage will range from 0.01-3% wt/wt in a suitable carrier. Theeffective dosage range of the pharmaceutically acceptable derivativescan be calculated based on the weight of the parent compound to bedelivered. If the derivative exhibits activity in itself, the effectivedosage can be estimated as above using the weight of the derivative, orby other means known to those skilled in the art.

In certain embodiments of the second aspect of the invention, thecomposition further comprises an agent, such as an antisenseoligonucleotide, that inhibits the expression of an HDAC gene. Thecombined use of a nucleic acid level inhibitor (e.g., antisenseoligonucleotide) and a protein level inhibitor (i.e., inhibitor of HDACenzyme activity) results in an improved inhibitory effect, therebyreducing the amounts of the inhibitors required to obtain a giveninhibitory effect as compared to the amounts necessary when either isused individually. The antisense oligonucleotides according to thisaspect of the invention are complementary to regions of RNA ordouble-stranded DNA that encode an HDAC gene. In other embodiments ofthe second aspect, the composition further comprises an additional agentthat inhibits the eznymatic activity of the HDAC enzyme.

Additional inhibitory agents may also be present in the compositions ofthis invention, where the combination causes no unacceptable adverseeffects.

Inhibition of HDAC Activity

In a third aspect, the invention provides a method of inhibiting HDACactivity, the method comprising contacting the HDAC with an inhibitioneffective amount of a compound according to the present invention, orwith an inhibition effective amount of a composition according to thepresent invention. Inhibition of HDAC activity can be in a cell or amulticellular organism. If in a cell, the method according to thisaspect comprises contacting the cell with an inhibition effective amountof a compound according to the present invention, or with an inhibitioneffective amount of a composition according to the present invention. Ifin a multicellular organism, the method according to this aspect of theinvention comprises administering to the organism an inhibitioneffective amount of a compound according to the present invention, or aninhibition effective amount of a composition according to the presentinvention. In certain embodiments, the organism is a mammal, forexample, a human. In certain embodiments, the method further comprisescontacting the HDAC or the cell, with an effective amount of anadditional inhibitory agent, or if in a multicellular organism,concurrently or sequentially administering an inhibition effectiveamount of an additional inhibitory agent.

In certain embodiments, the method is a method of treating a diseaseresponsive to an inhibitor of HDAC activity and comprises administeringto an individual in need thereof an effective amount of a compound orcomposition thereof according to the present invention. In certainembodiments, the method of treatment further comprises administering aneffective amount of an additional therapeutic agent, wherein theadditional therapeutic agent is a therapeutic agent appropriate fortreating the disease.

Because compounds of the invention inhibit HDAC activity they are usefulresearch tools for in vitro study of HDACs and their role in biologicalprocesses.

Measurement of the enzymatic activity of an HDAC can be achieved usingknown methodologies.

In some embodiments, the HDAC inhibitor interacts with and reduces theactivity of fewer than all HDACs in the cell. In certain embodiments,the inhibitor interacts with and reduces the activity of HDAC4, HDAC5,HDAC6, HDAC7, HDAC8 and/or HDAC9, alternatively HDAC4, HDAC5, HDAC6,HDAC7 and/or HDAC8. In certain other embodiments, the inhibitor has anIC₅₀ for HDAC8 which is lower than the IC₅₀ for HDAC4, HDAC5, HDAC6and/or HDAC7.

In certain embodiments of the present invention, the HDAC inhibitor ofthe present invention may be administered together with another HDACinhibitor known in the art or which will be discovered. Administrationof such HDAC inhibitor may be done sequentially or concurrently. Incertain embodiments of the present invention the compositions comprisean HDAC inhibitor of the present invention and/or an antisenseoligonucleotide and/or another HDAC inhibitor known in the art or whichwill be discovered. The active ingredients of such compositions forexample act synergistically to produce a therapeutic effect.

In another embodiment of the third aspect, the method comprisesinhibiting HDAC with a compound according to any of Formulae (I) to(Iaa) and Formula (II).

In another embodiment of the third aspect, the method comprisesinhibiting HDAC with a compound selected from the group consisting of

N-hydroxybiphenyl-2-carboxamide, N-hydroxy-2-phenoxybenzamide,N-hydroxy-2-(phenylamino)benzamide and 2-benzyl-N-hydroxybenzamide.

In another embodiment of the third aspect, the method of treating adisease responsive to an inhibitor of HDAC activity comprisesadministering to an individual in need thereof an effective amount of acompound according to any of Formulae (I) to (Iaa).

In another embodiment of the third aspect, the method of treating adisease responsive to an inhibitor of HDAC activity comprisesadministering to an individual in need thereof an effective amount of acompound selected from the group consisting of

N-hydroxybiphenyl-2-carboxamide, N-hydroxy-2-phenoxybenzamide,N-hydroxy-2-(phenylamino)benzamide and 2-benzyl-N-hydroxybenzamide,or a composition thereof.

The following Examples are intended to further illustrate certainembodiments of the invention, and are not intended to limit the scope ofthe invention.

Assay Examples Assay Example 1 Inhibition of Histone DeacetylaseEnzymatic Activity Inhibition of HDAC-1, 2, 3, 6 and 8

The following protocol is used to assay the compounds of the invention.In the assay, the buffer used is 25 mM HEPES, pH 8.0, 137 mM NaCl, 2.7mM KCl, 1 mM MgCl₂ and the substrate is Boc-Lys(Ac)-AMC in a 50 mM stocksolution in DMSO. The enzyme stock solution is 4.08 μg/mL in buffer.

The compounds are pre-incubated (2 μL in DMSO diluted to 13 μL in bufferfor transfer to assay plate) with enzyme (20 μL of 4.08 μg/mL) for 10minutes at room temperature (35 μL pre-incubation volume). The mixtureis pre-incubated for 5 minutes at room temperature. The reaction isstarted by bringing the temperature to 37° C. and adding 15 μLsubstrate. Total reaction volume is 50 μL. The reaction is stopped after20 minutes by addition of 50 μL developer, prepared as directed byBiomol (FLUOR DE LYS™ developer, Cat. #KI-105). A plate is incubated inthe dark for 10 minutes at room temperature before reading (λ_(Ex)=360nm, λ_(Em)=470 nm, Cutoff filter at 435 nm).

Inhibition of Class II HDAC and HDAC-11

A 30 mM stock of Boc-Lys(trifluoroacetyl)-AMC substrate is prepared inDMSO. 2 μL test compound in DMSO is diluted to 50 μL in buffer (25 mMHEPES, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl₂, 0.1% BSA) andpre-incubated with HDAC enzyme (30 μL of a final enzyme concentration of0.1-0.2 nM) for 10 minutes at room temperature. Reaction is started byadding 18 μL Boc-Lys(trifluoroacetyl)-AMC substrate and incubating at37° C. for 20-30 minutes. The reaction is stopped by adding 50 μLtrypsin (1 mg/mL) and a known HDAC inhibitor. The plate is thenincubated in the dark for 20 minutes at room temperature and read withEx=360 nm, Em=470 nm, cutoff filter at 435 nm.

Compounds exemplified have an IC₅₀ value less than or equal to 12 μMagainst one or more of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9 andHDAC11. The IC₅₀ values of some compounds according to the presentinvention are shown in Table 10. In the table, “a” represents an IC₅₀value of less than 250 nM against one or more of HDAC4, HDAC5, HDAC6,HDAC7, HDAC8, HDAC9 and HDAC11; 250 nM≦“b”<500 nM; 500 nM≦“c”<750 nM;750≦“d”<5000 nM.

TABLE 10 IC₅₀ Cpd IC₅₀ Cpd IC₅₀ Cpd No. IC₅₀ code Cpd No. code No. codeNo. code 13 d 108 d 125 a 147 a 19 d 109 a 130 a 181 a 21 d 110 a 131 c148 a 24 d 80 a 126 c 162 a 26 d 81 a 132 a 150 a 27 d 86 a 133 a 151 a50 d 89 b 139 d 152 a 33 c 92 a 140 c 153 b 98 c 116 a 141 b 154 c 29 c117 a 143 b 155 a 32 c 120 a 144 a 157 a 74 a 121 a 145 a 158 a 51 a 122a 180 a 160 b 52 a 105 c 146 a 106 b 104 a 182 a

While the invention has been described in connection with specificembodiments thereof, it will be understood that it is capable of furthermodifications and this application is intended to cover any variations,uses, or adaptations of the invention following, in general, theprinciples of the invention and including such departures from thepresent disclosure as come within known or customary practice within theart to which the invention pertains and as may be applied to theessential features hereinbefore set forth, and as follows in the scopeof the appended claims.

1.-43. (canceled)
 44. A compound of the formula (I):

and or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt,prodrug or complex thereof, in the form of a racemic or scalemicmixture, tautomer, diastereomer or enantiomer thereof, wherein

 is a five-membered heteroaryl; W is N or —C═; M is —C(O)N(H)OH; R¹ andR² is independently selected from the group consisting of —H, -alkyl,-aryl, -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl,alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroarylmoiety is optionally substituted; R is selected from the groupconsisting of H, alkyl, halo, hydroxy, nitro, C₁-C₄alkyl, —NR¹R², —OR¹,aryl, heteroaryl, alkyloxy and CF₃; n is an integer from 0 to 1; L isselected from the group consisting of aryl, heteroaryl, cycloalkyl,heterocyclyl, fused aryl, fused heterocyclyl, fused cycloalkyl,-alkenyl-aryl, -aryl-heteroaryl, -heteroaryl-aryl, -alkynyl-aryl,-alkyl-aryl, —SO₂—N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl, —CF₃, -t-Bu,—NR₁SO₂-aryl, halo, —N(R¹)C(O)-aryl and —S-aryl, wherein each aryl,heteroaryl, cycloalkyl and heterocyclyl moiety is optionally substitutedwith 1 to 3 independently selected substituents, and each of which isoptionally fused to one or more aryl, heterocyclic or heteroaryl rings,or one or more saturated or partially unsaturated cycloalkyl orheterocyclyl rings, each of which ring is optionally substituted,wherein a heteroaryl moiety in

 is optionally connected to a cycloalkyl, heterocyclyl, aryl orheteroaryl in L by a bond or by a bridging substituent; and Y isselected from the group consisting of halo, alkoxy, aryl, heterocyclyl,heteroaryl, —N(R¹)—C(O)-alkyl-aryl, —C(O)—N(R¹)-aryl-O-aryl,—N(R¹)—SO₂-aryl, -alkyl-aryl, -alkyl-heteroaryl, -aryl-heterocyclyl,-heterocyclyl-alkyl-aryl, heterocyclyl-alkyl-heteroaryl,-heterocyclyl-C(O)-aryl, —CH(aryl)₂, -heterocyclyl-C(O)-alkyl,-heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl,-heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,-heterocyclyl-alkyl-heteroaryl, -heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl,-alkyl-O-aryl, -alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R¹)-alkyl-aryl,—C(O)—N(R¹)-aryl, —N(R¹)—C(O)—O-alkyl-aryl, —N(R¹)—SO₂-alkyl-aryl,—N(R¹)—SO₂-aryl and —N(R¹)—SO₂-heteroaryl, wherein each aryl, heteroaryland heterocyclyl moiety is optionally substituted with 1 to 3independently selected substituents, and each of which is optionallyfused to one or more aryl, heterocyclic or heteroaryl rings, or one ormore saturated or partially unsaturated cycloalkyl or heterocyclylrings, each of which ring is optionally substituted, with the provisothat

is not isoxazol or pyrrole.
 45. The compound according to claim 44,having the Formula (Ia):


46. The compound according to claim 44, wherein

is selected from the group consisting of

wherein A¹, A², A³, A⁴ and A⁵ form a 5-membered heteroaryl ring, whereinA¹ and A³ are selected from the group consisting of carbon, nitrogen,—S— and —O—, A⁴ is carbon and A² and A⁵ are nitrogen or carbon, providedthat at least one of A² and A⁵ is carbon, and wherein * represents thepoint of attachment to group L and ** represents the point of attachmentto group Y.
 47. The compound according to claim 44, wherein n is
 0. 48.The compound according to claim 44, wherein L is aryl or heteroaryl,each of which is optionally substituted with 1, 2 or 3 independentlyselected substituents.
 49. The compound according to claim 44, wherein

is

n is 1; R is H; L is aryl or N(R¹)SO₂-aryl, wherein said aryl moiety isoptionally substituted with 1, 2 or 3 independently selectedsubstituents; Y is aryl, heteroaryl, or aryl-heterocyclyl, wherein saidaryl and heteroaryl moieties are optionally substituted with 1, 2 or 3independently selected substituents; and R¹ is H; wherein

represents the point of attachment to group M, * represents the point ofattachment to group L and ** represents the point of attachment to groupY.
 50. The compound according to claim 44, wherein W is —═; n is 0; L isselected from the group consisting of aryl, —N(R¹)C(O)-aryl, —CF₃,heteroaryl, —N(R¹)SO₂-aryl, -alkynyl-aryl, -alkyl-aryl,—SO₂—N(R¹)—C₀-C₄-alkyl-aryl, —N(R¹)-aryl, -heteroaryl-aryl,aryl-heteroaryl and fused heterocyclyl, wherein said aryl, heteroaryland fused heterocyclyl are optionally substituted with 1, 2 or 3independently selected substituents; Y is selected from the groupconsisting of aryl, halo, heteroaryl and -heterocyclyl-C(O)-alkyl,wherein said aryl and heteroaryl are optionally substituted with 1, 2 or3 independently selected substituents.
 51. The compound according toclaim 44, wherein W is —C═; n is 0; L is selected from the groupconsisting of aryl, —N(R¹)C(O)-aryl, —CF₃, heteroaryl, —N(R¹)SO²-aryl,-alkynyl-aryl, -alkyl-aryl, —SO²—N(R¹)—C₀-C₄-alkyl-aryl, —N(R¹)-aryl,-heteroaryl-aryl, aryl-heteroaryl and fused heterocyclyl, wherein saidaryl, heteroaryl and fused heterocyclyl are optionally substituted with1, 2 or 3 independently selected substituents; Y is selected from thegroup consisting of aryl, halo, heteroaryl and -heterocyclyl-C(O)-alkyl,wherein said aryl and heteroaryl are optionally substituted with asubstituent selected from the group consisting of alkyl, alkoxy andfused heterocyclyll.
 52. The compound according to claim 44, wherein Wis —C═; n is 0; L is selected from the group consisting of phenyl,—N(R¹)C(O)-aryl, —CF₃, heteroaryl, —N(R¹)—SO₂-aryl, -alkynyl-aryl,-alkyl-aryl, —SO₂—N(R¹)—C₀-C₄-alkyl-aryl, —N(R¹)-aryl, -heteroaryl-aryl,—S-aryl and fused heterocyclyl, wherein said aryl, heteroaryl and fusedheterocyclyl are optionally substituted with 1, 2 or 3 independentlyselected substituents; and Y is selected from the group consisting ofaryl, halo, heteroaryl, —N(R¹)—C(O)-alkyl-aryl, —C(O)—N(R¹)-aryl-O-aryl,dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one,—N(R¹)—SO₂-aryl, -alkyl-aryl, -alkyl-O-aryl, -aryl-heterocyclyl,benzo[d][1,3]dioxole, heterocyclyl, -heterocyclyl-alkyl-aryl,-heterocyclyl-C(O)-aryl, -2,3-dihydrobenzofuran,heterocyclyl-alkyl-heteroaryl, —CH-(aryl)₂, -heterocyclyl-C(O)—O-alkyl,-heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,-heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl, -alkyl-O—C(O)—N(R¹)-alkyl-aryl,-alkyl-N(R¹)-alkyl-aryl, —C(O)—N(R¹)-aryl, —N(R¹)—C(O)-alkyl-aryl,—N(R¹)—SO₂-aryl, —N(R¹)—SO₂-alkyl-aryl, —N(R¹)—SO₂-heteroaryl and-heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl areoptionally substituted with 1, 2 or 3 independently selectedsubstituents.
 53. The compound according to claim 44, wherein

 is selected from the group consisting of pyrazolyl, thiazolyl, thienyl,benzofuranyl, benzothienyl and pyrimidinyl; W is —C═; n is 0; L isselected from the group consisting of phenyl, —N(R¹)C(O)-aryl, —CF₃,heteroaryl, —N(R¹)—SO₂-aryl, -alkynyl-aryl, -alkyl-aryl,—SO₂—N(R¹)—C₀-C₄-alkyl-aryl, —N(R¹)-aryl, -heteroaryl-aryl, —S-aryl andfused heterocyclyl, wherein said aryl, heteroaryl and fused heterocyclylare optionally substituted with 1, 2 or 3 independently selectedsubstituents; and Y is selected from the group consisting of aryl, halo,heteroaryl, —N(R¹)—C(O)-alkyl-aryl, —C(O)—N(R¹)-aryl-O-aryl,dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one,—N(R¹)—SO₂-aryl, -alkyl-aryl, -alkyl-O-aryl, -aryl-heterocyclyl,benzo[d][1,3]dioxole, heterocyclyl, -heterocyclyl-alkyl-aryl,-heterocyclyl-C(O)-aryl, 2,3-dihydrobenzofuan,-heterocyclyl-alkyl-heteroaryl, —CH-(aryl)₂, -heterocyclyl-C(O)—O-alkyl,-heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,-heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl, -alkyl-O—C(O)—N(R¹)-alkyl-aryl,-alkyl-N(R¹)-alkyl-aryl, —C(O)—N(R¹)-aryl, —N(R¹)—C(O)-alkyl-aryl,—N(R¹)—SO₂-aryl, —N(R¹)—SO₂-alkyl-aryl, —N(R¹)—SO₂-heteroaryl and-heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl areoptionally substituted with 1, 2 or 3 independently selectedsubstituents selected from the group consisting of alkyl, alkoxy, —CF₃,optionally substituted phenyl, —N(R^(a))(R^(b)), —O-alkyl-morpholine andfused heterocyclyl.
 54. The compound according to claim 44, wherein

 is selected from the group consisting of pyrazolyl, thiazolyl, thienyl,benzofuranyl, benzothienyl and pyrimidinyl; W is —C═; n is 0; L isselected from the group consisting of phenyl, —N(R¹)C(O)-phenyl, —CF₃,benzothiazolyl, —N(R¹)SO₂-phenyl, -alkynyl-phenyl, thienyl, pyrrolyl,-alkyl-phenyl, pyridine, —SO₂—N(R¹)—C₀-C₄-alkyl-phenyl, —N(R¹)-aryl,-thienyl-phenyl, —S-phenyl and fused heterocyclyl, wherein said phenyl,benzothiazolyl, thienyl, pyrrolyl, pyridine and fused heterocyclyl areoptionally substituted with 1, 2 or 3 independently selectedsubstituents; and Y is selected from the group consisting of phenyl,halo, pyrrolyl, thienyl, —N(R¹)—C(O)-alkyl-phenyl,—C(O)—N(R¹)-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine,dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R¹)—SO₂-phenyl,-alkyl-phenyl, -alkyl-O-phenyl, pyridinyl, -phenyl-morpholine,benzothiophene, benzo[d][1,3]dioxole, piperidinyl,-piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl,2,3-dihydrobenzofuran, -piperidine-alkyl-pyridine, —CH-(phenyl)₂,-piperidine-C(O)—O-alkyl, -piperidine-SO₂-alkyl, -piperidine-SO₂-phenyl,-piperidine-alkyl-indole, -piperidine-SO₂-phenyl-N(R¹)—C(O)-alkyl,-alkyl-O—C(O)—N(R¹)-alkyl-phenyl, -alkyl-N(R¹)-alkyl-phenyl,—C(O)—N(R¹)-phenyl, —N(R¹)—C(O)-alkyl-phenyl, —N(R¹)—SO₂-phenyl,—N(R¹)—SO₂-alkyl-phenyl, —N(R¹)—SO₂-thienyl and -piperidine-C(O)-alkyl,wherein said phenyl, pyrrolyl, pyridinyl, benzothiophene, piperidinyl,indole and thienyl are optionally substituted with 1, 2 or 3independently selected substituents.
 55. The compound according to claim44, wherein

 is selected from the group consisting of pyrazolyl, thiazolyl, thienyl,benzofuranyl, benzothienyl and pyrimidinyl; W is —C═; n is 0; L isselected from the group consisting of phenyl, —N(R¹)C(O)-phenyl, —CF₃,benzothiazolyl, —N(R¹)SO₂-phenyl, -alkynyl-phenyl, thienyl, pyrrolyl,-alkyl-phenyl, pyridine, —SO₂—N(R¹)—C₀-C₄-alkyl-phenyl, —N(R¹)-aryl,-thienyl-phenyl, —S-phenyl and fused heterocyclyl, wherein said phenyl,benzothiazolyl, thienyl, pyrrolyl, pyridine and fused heterocyclyl areoptionally substituted with 1, 2 or 3 independently selectedsubstituents; and Y is selected from the group consisting of phenyl,halo, pyrrolyl, thienyl, —N(R¹)—C(O)-alkyl-phenyl,—C(O)—N(R¹)-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine,dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R¹)—SO₂-phenyl,-alkyl-phenyl, -alkyl-O-phenyl, pyridinyl, -phenyl-morpholine,benzothiophene, benzo[d][1,3]dioxole, piperidinyl,-piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl, 2,3-dihydrobenzofuan,-piperidine-alkyl-pyridine, —CH-(phenyl)₂, -piperidine-C(O)—O-alkyl,-piperidine-SO₂-alkyl, -piperidine-SO₂-phenyl, -piperidine-alkyl-indole,-piperidine-SO₂-phenyl-N(R¹)—C(O)-alkyl,-alkyl-O—C(O)—N(R¹)-alkyl-phenyl, -alkyl-N(R¹)-alkyl-phenyl,—C(O)—N(R¹)-phenyl, —N(R¹)—C(O)-alkyl-phenyl, —N(R¹)—SO₂-phenyl,—N(R¹)—SO₂-alkyl-phenyl, —N(R¹)—SO₂-thienyl and -piperidine-C(O)-alkyl,wherein said phenyl, pyrrolyl, pyridinyl, benzothiophene, piperidinyl,indole and thienyl are optionally substituted with 1, 2 or 3independently selected substituents selected from the group consistingof alkyl, alkoxy, —CF₃, optionally substituted phenyl, —N(R^(a))(R^(b)),—O-alkyl-morpholine and fused heterocyclyl.
 56. The compound accordingto claim 44, having the Formula (In):

wherein L is optionally substituted aryl; and Y is aryl,—C₀-C₃alkyl-aryl or heteroaryl, wherein said aryl and heteroarylmoieties are optionally substituted with 1, 2 or 3 independentlyselected substituents.
 57. The compound according to claim 44, havingthe Formula (Iq):

wherein L is optionally substituted aryl; and Y is selected from thegroup consisting of aryl, aryl-heterocyclyl, heteroaryl,-heterocyclyl-C₀-C₃alkyl-aryl, —C₀-C₃alkyl-heterocyclyl,-heterocyclyl-C₀-C₃alkyl-heteroaryl, -heterocyclyl-C(O)-alkyl, and—CH(aryl)₂, wherein each aryl, heterocyclyl and heteroaryl moiety isoptionally substituted with 1 to 3 independently selected substituents,and each of which is optionally fused to one or more aryl, heterocyclicor heteroaryl rings, or one or more saturated or partially unsaturatedcycloalkyl or heterocyclyl rings, each of which ring is optionallysubstituted with 1, 2 or 3 independently selected substituents.
 58. Thecompound according to claim 44, having the Formula (Iv):

wherein L is optionally substituted phenyl; Y is aryl, -alky-O-aryl,—C₀-C₃alkyl-aryl, -alkyl-O—C(O)—N(R¹)-alkyl-aryl,-alkyl-N(R¹)-alkyl-aryl and —C(O)—N(R¹)-aryl, wherein each aryl moietyis optionally substituted with 1 to 3 independently selectedsubstituents, and is optionally fused to one or more aryl, heterocyclicor heteroaryl rings, or one or more saturated or partially unsaturatedcycloalkyl or heterocyclyl rings, each of which ring is optionallysubstituted; and R¹ is selected from the group consisting of —H, -alkyl,-aryl, -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl,alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroarylmoiety is optionally substituted.
 59. A compound of the Formula (II):

and N-oxides, hydrates, solvates, pharmaceutically acceptable salts,prodrugs and complexes thereof, and racemic and scalemic mixtures,tautomers, diastereomers and enantiomers thereof, wherein L² is selectedfrom the group consisting of H, —C₀-C₃alkyl-aryl,—C₀-C₃alkyl-heteroaryl, —C₁-C₆alkyl, in which each aryl and heteroarylis optionally substituted with one, two or three substituentsindependently selected from halo, heterocyclyl, CF₃, amino, OCH₃ and OH;and Y is selected from the group consisting of H, halo, alkoxy, aryl,alkyl, heterocyclyl, heteroaryl, —N(R¹)—C(O)-alkyl-aryl,—C(O)—N(R¹)-aryl-O-aryl, —N(R¹)—SO₂-aryl, -alkyl-aryl,-alkyl-heteroaryl, -aryl-heterocyclyl, -heterocyclyl-alkyl-aryl,heterocyclyl-alkyl-heteroaryl, -heterocyclyl-C(O)-aryl, —CH(aryl)₂,-heterocyclyl-C(O)-alkyl, -heterocyclyl-C(O)-heterocyclyl,-heterocyclyl-C(O)—O-alkyl, -heterocyclyl-SO₂-alkyl,-heterocyclyl-SO₂-aryl, -heterocyclyl-alkyl-heteroaryl,-heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl, -alkyl-O-aryl,-alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R¹)-alkyl-aryl,—C(O)—N(R¹)-aryl, —N(R¹)—C(O)—O-alkyl-aryl, —N(R¹)—SO₂-alkyl-aryl,—N(R¹)—SO₂-aryl and —N(R¹)—SO₂-heteroaryl, wherein each aryl, heteroaryland heterocyclyl moiety is optionally substituted with 1 to 3independently selected substituents, and each of which is optionallyfused to one or more aryl, heterocyclic or heteroaryl rings, or one ormore saturated or partially unsaturated cycloalkyl or heterocyclylrings, each of which ring is optionally substituted; and M isC(O)—NH—OH.
 60. A composition comprising a compound according to claim44 and a pharmaceutically acceptable carrier.
 61. A method of inhibitingHDAC activity, the method comprising contacting the HDAC or a cellcomprising the HDAC with an inhibiting effective amount of a compoundaccording to claim 44 or a composition thereof.
 62. The method accordingto claim 61, wherein the HDAC is one or more of HDAC4, HDAC5, HDAC6,HDAC7, HDAC8, HDAC9 and HDAC11.
 63. A method of treating a diseaseresponsive to an inhibitor of HDAC activity, comprising administering toan individual in need thereof an effective amount of a compoundaccording to claim 44 or a composition thereof.
 64. The method accordingto claim 63, wherein the disease is responsive to an inhibitor of one ormore of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9 and HDAC
 11. 65. Amethod of inhibiting HDAC activity, the method comprising contacting theHDAC or a cell comprising the HDAC with an inhibiting effective amountof a compound or an N-oxide, hydrate, solvate, pharmaceuticallyacceptable salt, prodrug or complex thereof, in the form of a racemic orscalemic mixture, tautomer, diastereomer or enantiomer thereof, or acomposition of any of the foregoing, wherein the compound is selectedfrom # Structure  66

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66. The method according to claim 65 wherein the HDAC is one or more ofHDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9 and HDAC11.
 67. A compound ofthe formula (I):

and or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt,prodrug or complex thereof, in the form of a racemic or scalemicmixture, tautomer, diastereomer or enantiomer thereof, wherein

 is pyrrole; W is N or —C═; M is C(O)N(H)OH; R¹ and R² is independentlyselected from the group consisting of —H, -alkyl, -aryl, -aryl-aryl,-hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl, alkyl-heteroaryland -alkyl-aryl, wherein each aryl and heteroaryl moiety is optionallysubstituted; R is selected from the group consisting of H, alkyl, halo,hydroxy, nitro, C₁-C₄alkyl, —NR′R², —OR′, aryl, heteroaryl, alkyloxy andCF₃; n is an integer from 0 to 1; L is selected from the groupconsisting of aryl, heteroaryl, cycloalkyl, heterocyclyl, fused aryl,fused heterocyclyl, fused cycloalkyl, -alkenyl-aryl, -aryl-heteroaryl,-heteroaryl-aryl, -alkynyl-aryl, -alkyl-aryl,—SO₂—N(R¹)—C₀-C₄alkyl-aryl, —N(R¹)-aryl, —CF₃, -t-Bu, NR₁SO₂-aryl, halo,—N(R¹)C(O)-aryl and —S-aryl, wherein each aryl, heteroaryl, cycloalkyland heterocyclyl moiety is optionally substituted with 1 to 3independently selected substituents, and each of which is optionallyfused to one or more aryl, heterocyclic or heteroaryl rings, or one ormore saturated or partially unsaturated cycloalkyl or heterocyclylrings, each of which ring is optionally substituted, wherein aheteroaryl moiety in

 is optionally connected to a cycloalkyl, heterocyclyl, aryl orheteroaryl in L by a bond or by a bridging substituent; and Y isselected from the group consisting of halo, alkoxy, aryl, heterocyclyl,heteroaryl, —N(R¹)—C(O)-alkyl-aryl, —C(O)—N(R¹)-aryl-O-aryl,—N(R¹)—SO₂-aryl, -alkyl-heteroaryl, -aryl-heterocyclyl,-heterocyclyl-alkyl-aryl, heterocyclyl-alkyl-heteroaryl,-heterocyclyl-C(O)-aryl, —CH(aryl)₂, -heterocyclyl-C(O)-alkyl,-heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl,-heterocyclyl-SO₂-alkyl, -heterocyclyl-SO₂-aryl,-heterocyclyl-alkyl-heteroaryl, -heterocyclyl-SO₂-aryl-N(R¹)—C(O)-alkyl,-alkyl-O-aryl, -alkyl-O—C(O)—N(R¹)-alkyl-aryl, -alkyl-N(R¹)-alkyl-aryl,—C(O)—N(R¹)-aryl, —N(R¹)—C(O)—O-alkyl-aryl, —N(R¹)—SO₂-alkyl-aryl,—N(R¹)—SO₂-aryl and —N(R¹)—SO₂-heteroaryl, wherein each aryl, heteroaryland heterocyclyl moiety is optionally substituted with 1 to 3independently selected substituents, and each of which is optionallyfused to one or more aryl, heterocyclic or heteroaryl rings, or one ormore saturated or partially unsaturated cycloalkyl or heterocyclylrings, each of which ring is optionally substituted.